EP3265961A1 - Authenticated systems employing fluorescent diamond particles - Google Patents

Abstract

Authentication systems for products employing populations containing particles of diamonds that have fluorescent emissions of various wavelengths, intensities and durations are described. By varying the populations of diamond particles in products to be labeled, multiple different identification systems can be obtained permitting authentication taggants for large numbers of different products. The use of diamond microparticles (diamond powder) for authenticating, identifying and constructing anti-counterfeiting systems pharmaceuticals, including but not limited to solid oral dosage forms, liquids, syrups, creams, and powders; as well as prestige cosmetics and fragrances, high-end wines and spirits (liquor), foods, textiles, paints, inks, currency, stamps (e.g., tax stamps), mechanical parts and packaging is described.

Description

AUTHENTICATION SYSTEMS EMPLOYING FLUORESCENT DIAMOND PARTICLES

PRIORITY BENEFIT

This application claims the benefit of U.S. provisional application No. 62/127,266, filed on March 2, 2015, U.S. provisional application No. 62/128,409, filed on March 4, 2015, and U.S. provisional application No. 62/128,930, filed on March 5, 2015, each of which is incorporated herein by reference in its entirety.

1. TECHNICAL FIELD

[0001] The invention relates to the field of anti-counterfeiting systems that can be incorporated into various products, including pharmaceutical products and other materials such as textiles, mechanical parts, electronic parts, inks, paint, currency, cosmetics and fragrances, luxury items, wines and spirits (liquor), and food. In particular, it relates to such systems that employ

populations of diamond particles that when exposed to appropriate sources of electromagnetic radiation fluoresce at certain wavelengths with certain intensities for certain periods of time.

2. BACKGROUND

[0002] Numerous approaches have been employed to prevent counterfeiting in a wide variety of products, including imprinting designs, adding colorants, electronic microchips, and a vast array of alternatives. Many of these rely on the laboratory determination of embedded signature arrays, developable colors, microscopic surface patterns, internal patterns of letters, numbers and barcodes, or the use of complex optical imaging systems.

[0003] For example, U.S. 7,394,997 describes a "consumable" having taggant nanoparticles which particles have a plurality of different characteristics of different categories. The focus of this application is on inks or toners designed to be compatible with specific printers.

[0004] A particularly important and challenging area for counterfeit detection is the

pharmaceutical arena. Obviously, the harm caused by counterfeited drugs is significantly more serious than the use of an unauthorized toner or ink in a printer. Many strategies have been employed. A family of U.S. patents: U.S. 7,874,489; U.S. 8,220,716 and U.S. 8,458,475 describe compositions that are labeled by a product authentication code which is a signature array, where the signature array comprises information about the absolute counts or relative counts of entities of at least two distinct clusters of entities. The method thus relies on determining the numbers of individual elements in sets of populations.

[0005] U.S. publication 2001/0014131 suggests a method to identify pharmaceutical products by stamping patterns on their surfaces with lateral dimensions smaller than about 100 μ. A similar approach is described in US2010/0297228 as well as in US2010/0297027. US2009/0304601 describes a method for marking a composition for use in oral administration using color-inducing oxides in the composition. US2007/0259010 employs printed dosage forms with internal patterns that can be used for authentication, including letters, numbers and bar codes.

[0006] US2007/0048365 discloses edible coatings for pharmaceuticals that can be imprinted with codes that are machine-readable. US2006/0118739 describes pharmaceuticals that have luminescent markers with a spectral signature characteristic of the authentic product.

U.S. 8, 144,399 utilizes a complex optical image system for identification of genuine

pharmaceutical products. U.S. 8,069,782 uses stamped patterns as identification for solid pharmaceuticals. U.S. 7,619,819 employs an optical system that utilizes diffraction gratings.

[0007] US2013/0072897 employs electromagnetic transmitters and receivers for determining identity of a drug reservoir. Visible radiation may also be used.

[0008] Despite the available options for authentication, including imprints, colorants, electronic microchips, inert materials and other alternatives, counterfeiting remains a major problem in pharmaceutical manufacturing.

3. SUMMARY OF THE INVENTION

[0009] The invention relates to the use of diamond particles (diamond powder) for

authenticating, identifying and constructing anti-counterfeiting systems for pharmaceuticals, including but not limited to solid oral dosage forms, liquids, syrups, creams, and powders; as well as cosmetics and fragrances, wines and spirits (liquor), softdrinks, foods, textiles, paints, inks, currency, stamps (e.g., tax stamps), mechanical parts, electronic components and packaging.

[0010] The invention is based, in part, on exploiting the natural variations in the carbon lattice structure of diamond that cause it to emit fluorescence when exposed to certain sources of electromagnetic radiation. An almost infinite number of lattice structure variations (and fluorescent emissions) are possible. Moreover, diamond particles are inert, stable, and nontoxic. They can be used to produce hundreds of thousands of encrypted signatures, and are effective in trace amounts - - i.e., only 0.01-0.001% of the product is required to be labeled; or even 1 ppm or 0.0001% as a lower limit. The lowest limit needed for detection depends on the sophistication of the detector and thus considerably lower levels could also be detected with the appropriate equipment.

[0011] For example, diamond preparations can be used to provide identification indicia (i.e., signatures arrays) unique to a specific product, or product lot. This is because different, random mixtures of diamond particles can be created which fluoresce at various wavelengths when exposed to certain sources of electromagnetic radiation, each with various intensities and each for various periods of time. These variations result from slight differences in the carbon lattice architecture that define diamond. They do not otherwise affect its chemical or physical properties, stability, inertness or lack of toxicity.

[0012] The preparation of diamond particle populations with a defined emission for use in the authentication system is described. The authentication system incorporated with (into or on) a product comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

[0013] In accordance with the invention, these diamond particle preparations can be used to authenticate product on a covert basis - by encrypting the product with a signature signal invisible to the naked eye that can be made visible (or read) using a hand held or other device that generates the electromagnetic radiation required for the diamonds to fluoresce. The same signature signal can be encrypted on the product's packaging, its label and/or barcode. Alternatively, the diamond particles can be used for encryption on a forensic basis - requiring laboratory testing or

sophisticated equipment to detect the signature signal. In yet another approach, a combination of covert and overt systems can be used - for example where the diamond particles are added to color shifting ink used in or on the product, on its packaging and/or barcode label. See, for example, the system described in Section 5.3.3.

[0014] Illustrative embodiments of the authentication system of the invention are described infra, for authenticated pharmaceuticals (Section 5.4), including but not limited to formulations such as authenticated tablets (Section 5.4.1), authenticated syrups (Section 5.4.2), authenticated capsules (Section 5.4.3), authenticated creams (Section 5.4.4), authenticated injectable drugs (Section 5.4.5), authenticated powders (Section 5.4.6), authenticated suppositories (Section 5.4.7), authenticated aerosols (Section 5.4.8), and authenticated ophthalmic preparations (Section 5.4.9); as well as authenticated goods (Section 5.5) and cosmetics and fragrances, including but not limited to authenticated perfumes (Section 5.5.1) and authenticated wines and liquors (Section 5.5.2).

[0015] The invention is illustrated by examples that describe the preparation of diamond particles (Example 1); simple labeling of solid dosage forms (Example 2); the visual appearance of fluorescent emissions from diamond populations in suspension (Example 3); the emission spectra of the separated red, green and blue particle populations (Example 4); the visibility on dosage forms (Example 5); comparisons of variously labeled tablets (Example 6); the manufacture of a film coated tablet (Example 7); liquid formulation for oral administration (Example 8); film tab for mucosal administration (Example 9); nasal spray for mucosal delivery (Example 10); lotion for topical administration (Example 11); and liquid formulation (biologic) for intravenous

administration (Example 12).

[0016] The invention also relates to hand held mobile remotely programmable detection devices that can be used to authenticate genuine product at any point in the distribution chain.

3.1. DEFINITIONS

As used herein, the following terms shall have the meanings indicated.

[0017] "Microparticles" means particles of diamond that have average diameters in the range of 1 μ to 1 mm, more typically 1 μ to 100 μ.

[0018] "Nanoparticles" refers to diamond particles that have diameters between 1 nm and 1,000 nm, typically in the range of 10 nm-500 nm or 10 nm-100 nm.

[0019] The term "particles" or "diamond particles" includes microparticles and nanoparticles.

[0020] Specific "populations" of diamond particles may be heterogeneous or homogeneous. By a homogeneous population is meant a collection of particles that all have the same excitation and emission spectrum. By the same spectrum is meant that the location of the excitation and emission wavelengths and the intensity and duration of emission based on a particular intensity and duration of excitation is the same for all members of the population within a range sufficiently small that the population is discernible as a distinct population. The level of homogeneity will depend on the manner in which the populations are to be used.

[0021] The "prescribed form" of the authentication system refers to the particular population or mixtures of populations of diamond particles that are used in a particular authentication system with respect to a particular product. The product to be analyzed will either have the prescribed form contained within it, in which case it is indeed authentic, or it will have no authentication system or a different authentication system in which case it is not authentic. The product or packaging to be tested will be tested for this prescribed form, and it may or may not in fact contain it. The prescribed form is typically designed by the manufacturer or by a supplier and under the control of the designer. Because the authentication systems consist entirely of inert diamond material regardless of the proportions of any of the various populations in the prescribed form, the designer is at liberty to select from a multitude of possible variations.

[0022] As used herein, "product" or "substrate" refers to the material which is to be authenticated. Thus, whether the product or substrate is a tablet, a piece of cloth, a solid article, a powder or a liquid composition, an emulsion or a semisolid, an appropriate authentication method employing the diamond particles of the invention can be designed. "Product" also includes packaging, as well as intermediates which are to be converted to product. For example, if the product is a finished pharmaceutical dosage, the active pharmaceutical ingredient (API) may be labeled. Any intermediate that is carried over to the final product can be labeled.

[0023] One particularly useful embodiment relates to "solid oral dosage forms" or SODF's for which the FDA has issued guidelines for authentication using physical-chemical identifiers.

SODF's include without limitation, tablets, capsules containing powders, gels and the like.

[0024] As used herein, articles such as "a", "an" and the like are generally used to mean either one or more than one unless otherwise indicated. Further, where ranges of parameters are disclosed, where the ranges include integers, all integers within the cited range are included as if specifically set forth. For example, a range of variation of 4-10 possible intensities would specifically include variations that include 5, 6, 7, 8 or 9 different intensities. This stipulation is in order to avoid repetitious explicit enumeration and make the present specification more readable.

4. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.

[0026] Figure 1 shows a color photo of separated populations of red, green and blue diamond particles viewed under UV light.

[0027] Figure 2 is a color photo of an oral dosage form to which red, green and blue diamond particles have been affixed as viewed under ultraviolet light. [0028] Figure 3 is a color photo of a blister pack of dosage forms to which diamond particles have been added and viewed under ultraviolet light.

[0029] Figure 4 is a color photo of cuvettes containing particle suspensions of red or green, or red-green mixtures or red/green/blue mixtures viewed under ultraviolet light.

[0030] Figure 5 shows the visible emission spectra upon UV excitation of single color (red, green or blue) particles.

[0031] Figure 6 shows the visible emission spectrum upon UV excitation of mixtures of these particles.

[0032] Figure 7 shows solid dosage forms doped with red, green or blue particles.

[0033] Figure 8 shows the IR emission spectrum upon excitation with visible light of unseparated mixtures of diamond nanoparticles integrated into a solid substrate.

[0034] Figure 9 shows the visible emission spectrum obtained from such mixtures upon excitation with a wavelength of 365 nm.

[0035] Figure 10 is a photograph of nine different tablets composed of standard pharmaceutical excipients which have been tagged with various fluorescence colors of diamond particles or mixtures thereof.

[0036] Figure 1 1 shows a composite of spectra obtained individually from the tablets that contain red fluorescent particles only, green fluorescent particles only and blue fluorescent particles only.

[0037] Figure 12 is the emission spectrum between 400 and 700 nm of tablets that contain mostly red fluorescent particles but also a trace of green and blue.

[0038] Figure 13 is an expanded depiction of the portion of the spectrum in Figure 12 between 400 and 550 nm.

[0039] Figure 14 is a composite showing the spectrum of each of the nine tablets shown in Figure 10 over the 400-700 nm range.

[0040] Figure 15 shows the integrated forms of either the entire emission range in terms of total intensity counts or over the individual peaks defined by the individual components.

[0041] Figure 16 shows one embodiment of a system for authenticating and verification of authentication of products through stored data and algorithms.

[0042] Figure 17 shows a visible- visible spectrum where excitation light is blue and emission is red. [0043] Figure 18 diagrammatically illustrates the versatility of the authentication system. Every product/batch can be encrypted with unique coding— hundreds of thousands of encrypted signatures are possible. The encrypted signature in the product (tablets in the figure) is the same signature used to encrypt the barcode and/or the label on the bottle or package. The system does not necessarily depend on the barcode, as any part of the package labeling may contain encryption. As shown in the figure, the product can be directly authenticated both before and after removal from the package, including the ability to confirm authenticity through opaque packaging. The use of a handheld device to "read" the encrypted signal is depicted. Product authentication can also be accomplished remotely.

5. DETAILED DESCRIPTION OF THE INVENTION

[0044] The invention provides an authenticating system that is useful in a wide variety of products. The basis for this system is a population of particles of diamond that exhibit specific spectra or colors whereby suitable wavelengths, intensities and durations of emission are associated with a specific excitation wavelength of suitable intensity and duration, where previously determined emission spectral data are associated with the population. The excitation may be a one- photon or a two-photon excitation. Diamond particles also have detectable magnetic properties, which can add an extra level of forensic encryption. In view of the benign and inert nature of diamond particles and in view of the variety of spectral characteristics that can be achieved and associated with specific populations of such particles, diamond particles provide an excellent system for authentication of various products including pharmaceutical products and other materials such as textiles, inks, paint, currency, cosmetics, luxury items, fragrances or food.

5.1. DIAMOND PREPARATIONS USED IN THE AUTHENTICATION SYSTEMS

[0045] Diamond is a geometrical arrangement of carbon, in which individual carbon atoms form a specific lattice structure. Diamond can either occur naturally, or be produced synthetically by subjecting carbon atoms to high temperature and pressure (HTHP), detonating carbon in a closed environment to produce detonation nanodiamonds (D D), or by chemical vapor deposition (CVD), causing carbon vapors to coalesce into diamond.

[0046] It has long been known that both natural and synthetic diamond can emit fluorescence. This fluorescence occurs because of minor variations in the diamond carbon lattice structure due to the incorporation of trace amounts of atoms other than carbon— principally nitrogen— into this structure. Diamond is known to produce characteristic and unique spectral fingerprints. These fingerprints relate both to the wavelength of light used to excite diamond to produce fluorescence, and the wavelength, intensity and duration of the fluorescent light emitted. Both natural and synthetic diamonds efficiently produce intense, red, green, blue and infrared fluorescence. In addition, diamond particles have magnetic properties which can be detected by methods including, but not limited to, electron paramagnetic resonance (EPR) spectroscopy (also known as electron spin resonance (ESR) spectroscopy).

[0047] Because the signature produced by any population of diamond particles or mixture of diamond particles is dependent on diamond lattice structure, and an almost infinite number of variations in this structure are possible, diamond is capable of generating an extremely large number of spectral signatures in both the visible and infrared range, to say nothing of its detectable paramagnetic signatures.

[0048] This property, together with its inertness and stability, endow diamond with almost limitless complexity, unique utility as an encryption taggant and distinguish it from other materials that are used as taggants— for instance those that are used to authenticate packaging.

[0049] Diamond particles suitable for use in the authentication systems of the invention may be prepared by methods well known to those skilled in the art. The reports cited in the following discussion of such diamond preparations are each incorporated by reference herein in its entirety.

[0050] Both natural and synthetic diamonds emit fluorescence and can be used in the authenticating systems of the invention. A review by Walker, J., Rep. Prog. Phys. (1979)

42: 1607-1654 describes in detail the excitation and emission characteristics of various types of diamonds having impurities such as boron and nitrogen. As noted by the reviewer, these are the most common impurities in diamond. Boron leads to utility in some instances in semiconductor applications. Nitrogen results in defects that permit excitation by both visible and infrared light as well as by UV light and corresponding emissions. This article explains an idealized symmetry of the Stokes shift whereby a lower energy light is symmetrically emitted from a higher frequency absorption. The transition where vibrational states are zero in both electronic ground and excited state can be discerned in the fluorescence spectrum as the zero phonon line (ZPL) which is characteristic of a particular Stokes shift and can be used to identify diamond.

[0051] In addition to the Stokes shift, single diamond nanoparticles also show two photon excitation patterns wherein two photons of infrared light result in emission of visible wavelengths. See, Chang, Y.-R., et al., Nature Nanotechnology (2008) 3 :284-288, which describes the production and imaging of fluorescent nanodiamonds. U.S. patent No. 8,168,413 also describes this method for preparing luminescent diamonds, which is done by irradiating diamond particles of 1 nm to 100 nm with high energy and heating the resultant. The resulting diamonds have oxidized surfaces and contain 5 ppm to 1,000 ppm color centers.

[0052] Alternative methods described in US2010/0135890 can be used to produce diamonds in the microparticle range. The production of nitrogen vacancy centers (NV centers) responsible for the fluorescence in these cases is also described by Baranov, P. G., et al, Small

(2011) 7: 1533-1537.

[0053] Numerous types of color centers that have been described and exist in both natural and synthetic diamond particles, as shown in Table 1, can be used in the authenticating system.

Table 1

Excitation Emission ZPL

Publication / Source λ max (nm) λ max (nm) (nm) negative NV ^a 560 700 637 neutral NV ^a 532 575

N-V-N (H3) ^b 531 503

N₃ ^C (blue) 415 hydrogen enriched ^d (yellow)

boron enriched ^e 636-666

two photon emission ^a 1100 700

a) U.S. 8, 167,413

b) Yu, et al, JACS (2005) 127: 17604-17605

c) Chenko, et al, Nature (1977) 270:414-144

d) Fritsch, et al, Genes & Geniol (1992) 28:35-42

e) Steed, J. W., J. Appl Phys. (2003) 94:3091-4009

[0054] In addition, counterpart carbon nanoparticles that fluoresce in the visible range, as described in U.S. publication 2012/0178099 can be used. These are doped carbon particles (FCN's) that have fluorescent quantum yields in the range of 5-15% and emission colors at 455 nm (excitation at 350 nm), 480 nm (excitation at 400 nm), 520 nm (excitation at 400 nm), 540 nm (excitation at 450 nm) and 590 nm (excitation at 500 nm). Thus, five different combinations of excitation emission peaks are available. [0055] These FCN particles are capable of conjugation to biological molecules as are nanoparticle diamond complexes in US2010/0305309.

[0056] Importantly, in addition to these technical and precise parameters of diamond particles that can be used in authentication systems of considerable sophistication, a simpler approach is permitted by virtue of the ability of commercially available diamonds to emit various colors upon excitation with ultraviolet (UV) light. A commonly available LED source which emits light at 360 nm (and is not harmful to the eyes) has been shown to elicit red, green, blue and IR

fluorescence in commercially available diamond particles. Thus, a very straightforward authentication method can use combinations of these populations of diamonds in various ratios or simply alone, perhaps in a particular symbol or set of patterns.

[0057] A distinct advantage of using the diamond particles in the authentication system of the invention is that they are not cytotoxic. Indeed, diamond particles are used in dental polishing, and various publications have indicated that they can be used without cytotoxicity in biological systems. Schrand, A. M., et al, J. Phys. Chem. (2007) 111 :2-7 showed that nanodiamonds ranging in size from 2-10 nm were not cytotoxic to a variety of cell types. Mohan, N., et al, Nano. Lett. (2010) 10:3692-3699 showed that fluorescent nanodiamonds were stable and nontoxic in

C. elegans.

[0058] In sum, in view of the benign and inert nature of diamond particles and in view of the variety of spectral characteristics that can be achieved and associated with specific populations of such particles, diamond particles provide an excellent system for authentication of various products including pharmaceutical products and other materials such as textiles, inks, paint, currency, cosmetics, luxury items, fragrances or food.

5.2. THE AUTHENTICATION SYSTEMS

[0059] In its simplest form, a prescribed form of an authentication system comprising these particles and corresponding emission spectral characteristics are associated with the product, the presence of which indicates the authenticity of the product per se. In some embodiments, the presence of the prescribed forms of the authentication system is verified by excitation by a specific wavelength of specific intensity and duration combined with the intensity and/or duration of emission at selected wavelengths. In one embodiment, by coding the wavelength, intensity and duration of the excitation energy and providing this to the user, the manufacturer will permit the user to verify the authenticity of the product on site or by submission to a service provider based on the resulting emission signature.

[0060] In the alternative, a single excitation wavelength may generate different emission wavelengths and intensities depending on the nature of the diamond particles in the composition. As noted above, an ultraviolet light source emitting 360 nm can elicit red, green, blue or infrared (TR) fluorescence depending on the collection of diamond particles employed. A random mixture of such diamonds can be separated into various colors of emission by flow cytometry. ("Colors" includes UV, visible and IR emissions.) In general, "color" refers to the nature of fluorescence emissions— e.g., "green" refers to green fluorescence. A homogeneous population of such particles will provide a single color, though the complete spectrum will be more complex.

[0061] Thus, in one aspect, the invention is directed to a method for providing authentication to a product which method comprises combining said product with a prescribed form of an

authentication system (composition) which contains at least one population of diamond particles wherein said particles exhibit fluorescence with a fluorescence maximum at a particular

wavelength, and wherein the wavelength, intensity and duration of the fluorescence of said particles is dependent on the wavelength, duration and intensity of the excitation energy.

[0062] In order to provide a variety of possible identification patterns, it is also advantageous to use more than one homogeneous population of said particles so that a multiplicity of different authenticating labels can be generated by varying the proportion of these populations in the resulting product. The populations will differ in excitation and emission spectral data i.e.

wavelength, intensity and duration. Variations in this pattern may be obtained by varying the wavelength, intensity and duration of the excitation energy. Thus, the invention is also directed to a method for providing authentication by combining the product with a prescribed authentication system containing at least two homogeneous populations of particles wherein the wavelength, intensity and duration of the excitation and emission fluorescence is unique to each different population.

[0063] Still another level of authentication can be provided by including as a portion of the taggant (or as all of the taggant) unseparated diamond mixtures, i.e., a heterogeneous population. These mixtures appear non-fluorescent to the naked eye due to the cancellation of the fluorescence of the various components and the complexity of their interaction. However, excitation in the visible (or UV) light will result in a characteristic infrared spectrum which is difficult to duplicate using any counterfeit labeling that is different from heterogeneous populations of diamond particles, since these may vary from one such population to another. Thus, still another aspect of the invention is directed to substrates that are tagged entirely or in part with an unseparated mixture of fluorescent diamond nanoparticles. The invention also includes authenticating these substrates by determining an IR spectrum based on visible or UV excitation. In those situations where a heterogeneous population does not emit color, an IR signal may be used for authentication. In those situations where a homogeneous population does emit color, an IR signal may also be used for authentication.

[0064] In still another embodiment, the invention includes substrates tagged with diamond particles which substrates are comprised primarily of hydrophilic solid components, but further include a hygroscopic hydrophobic component. Upon application of pressure, the hydration water associated with the hygroscopic component is expelled creating an environment wherein diamond particles are unevenly distributed among the hydrophilic components and the hydrophobic dehydrated hygroscopic component. This redistribution is characteristic of diamond particles and is difficult to duplicate with substitute fluorescent materials. Thus, materials of this composition are also included within the invention and their characteristic "speckled" appearance in the presence of the diamond particles they contain is helpful in ascertaining the authentic nature of the substrate.

[0065] In some important embodiments, the product is a pharmaceutical, especially a solid oral dosage form, but the invention is useful in a wide variety of products. Here, diamond particles have the advantage of being completely inert and thus do not interfere with the desired properties of the product, such as the mode of action and pharmacokinetics and pharmacodynamics of

pharmaceutical products. Diamond particles have no effect on absorption, distribution, metabolism or elimination (ADME) and are not toxic.

[0066] In one embodiment, a population of particles that has a distinct emission spectrum when subjected to, for example, ultraviolet radiation is supplied. This may be a prescribed defined mixture of homogeneous populations of particles that have various levels of color centers of various types. The authentication in this case involves irradiation with ultraviolet light, and examining the spectrum or intensities, durations and wavelengths of emission and matching these with data supplied by the manufacturer. This may be done by having the user or purchaser obtain the spectrum or spectral data using a detector, supplied by the manufacturer or otherwise made available to the purchaser, to obtain the spectrum or emissions which can then be evaluated on site or electronically transmitted to a data center for verification— typically using a programmed interrogation device. Correlating a product identification number with spectral data and comparing the spectral data of the tested product to the data for the authentication system programmed into an interrogation device allows verification of authenticity and if done at a data center (based on electronically conveyed product spectral data) allows the data center to notify the user of the authenticity of the product. For example, a pharmacist purchasing an oral dosage form of a drug would expose the dosage form to a detector that obtains these spectral data and transmits them electronically to the data center. Alternatively, the detection function and interrogation function are integrated in the same device or apparatus, which may be programmed to use only certain excitation parameters and/or to detect only certain emission parameters.

[0067] In one embodiment, illustrated in the examples below, a preparation of diamond particles is separated into populations each of which emits a distinctive color, such as red, yellow, green or blue by any convenient method, such as flow cytometry. Irradiation with ultraviolet light of the appropriate wavelength will then effect emission of an individual color from each separate population. These populations in prescribed mixtures can be applied to products and their presence detected with the naked eye, as well as by precise spectra. By varying the patterns or ratios of the individual colors, various authentication codes one for each prescribed form of the authentication system will result. For example, both green particles and red particles could be applied in one case or green particles and blue particles in another, or simply red or simply green or simply blue in various proportions. It is sometimes helpful to have the various populations arranged in a pattern on a surface of the substrate so that the variation in the pattern is also distinctive, although in some cases overlap permits distinction— e.g., yellow and blue appears green. Differing intensities could also be employed as distinguishing feature, although if the naked eye is relied upon to distinguish intensities, the number of intensity levels available may be relatively small. Nevertheless, a wide number of authentication patterns can be employed using various combinations of these

populations as individual prescribed forms of the authentication system. In yet another

embodiment, the invention includes a heterogeneous population of diamond particles, with the proviso that the heterogeneous population is not applied on the product to mark the product with a pattern.

[0068] Alternatively, a system that permits the purchaser to identify the product on the site of purchase or use involves matching the excitation wavelengths, intensities and durations to the emission wavelengths, intensities and durations according to a code included in the packaging or otherwise associated with the product. [0069] In this more complex form, the code would inform the purchaser of the correct intensity and duration of the excitation wavelength such as that provided in Table 1 and the expected observed color, which would be visible at its relevant intensity to the naked eye. This could be done using a single population of particles, or a set of two or more homogeneous populations thus permitting a wider variety of fingerprints that could be discernible by the purchaser. This embodiment also may employ identification and verification by a data center after transmission of the spectrum or spectral data of the product which putatively contains the prescribed form of the authentication system to an interrogation device in the data center. The interrogation device could be a computer programmed to compare authentic spectral data to the data received. As described below, by varying not only the emission wavelengths, but employing ZPL determination, and/or intensity and/or duration determinations, a large number of distinct fingerprints can be generated. The distinction, however, may not be immediately discernible by the naked eye, but would require determination of the emission maximum wavelengths or ZPL's and/or intensities and/or duration in a more complex manner, and comparison could be made by a handheld interrogation device that compares spectral data of the prescribed form to the product spectrum on site or at a data center.

[0070] The invention is also directed to compositions prepared by the invention method as well as to methods of authentication which involve irradiating a product to be authenticated with the appropriate excitation wavelength of appropriate intensity and duration to generate fluorescence and to observe the fluorescence. Typically, the energy of excitation is higher than that of the emitted wavelength although by using two photon excitations the sum of the photons represents the excitation energy and thus the wavelength of each photon in the excitation spectrum may be longer than the wavelength of the emitted energy. Typical spectral emission in the visible range results from irradiation with ultraviolet light, although visible- visible emission excitation is also known (see Figure 17), as is two photon excitation from the IR to result in visible emission. Other anti- Stokes shifts such as conversion of infrared light to ultraviolet light are also known. The converse absorption generated Stokes shifts are also known, for example, conversion of ultraviolet light to infrared light, visible light to infrared light, or visible light to ultraviolet light. Ultraviolet to ultraviolet light and infrared to infrared excitation and absorption are also possible. The observation may be direct visual observation with the naked eye or may involve a complex spectrum generated by the appropriate excitation energies, and determined by a detector which may be a spectrophotometer and compared to an authentic spectrum by eye, or may employ a programmed detector that includes an interrogation device. In another embodiment, the method of authentication involves detection of magnetic properties of the tagged product through methods known to one skilled in the art, including but not limited to, electron paramagnetic resonance (EPR) spectroscopy (also known as electron spin resonance (ESR) spectroscopy).

5.3. MODES OF CARRYING OUT THE INVENTION

[0071] The invention provides an authentication system for a wide variety of products including pharmaceuticals, paints, oils, textiles, currency, food, and a multiplicity of other products that can be formulated to include diamond particles. For many applications, it may be useful to employ microparticles or nanoparticles. "Microparticles" means particles of diamond that have average diameters in the range of 1 μ to 1 mm, more typically 1 μ to 100 μ. "Nanoparticles" refers to diamond particles that have diameters between 1 nm and 1,000 nm, typically in the range of 10 nm-500 nm or 10 nm-100 nm. In some applications, a particular size of particles may be preferred. Microparticles, for example, may be appropriate for orally administered compositions. Particles in the micron range have been shown to fluoresce, perhaps more brightly than those in the nanometer range, by, for example, Bradac, et al., Nano Lett. (2009) 9:3555-3564; Boudou, J. -P., et al., Nanotech. (2009) 20:235602.

[0072] The size of the particles useful will depend on the particular application. For example, in the context of currently available printing equipment, typically, particles should be no larger than 5 microns. For use in pharmaceutical tablets, for example, a typical size might be approximately 100 nm. There is no hard and fast rule, however, and these are merely suggested sizes. It will be apparent to the practitioner for a particular application what range of sizes is suitable.

[0073] Also important to the invention is the definition of specific "populations" of diamond particles. The population may be heterogeneous or homogeneous. By a homogeneous population is meant a collection of particles that all have the same excitation and emission spectrum. By the same spectrum is meant that the location of the excitation and emission wavelengths and the intensity and duration of emission based on a particular intensity and duration of excitation is the same for all members of the population within a range sufficiently small that the population is discernible as a distinct population. The level of homogeneity will depend on the manner in which the populations are to be used. For example, if all that is necessary is to separate the particles into populations of different colors that are distinguishable by the naked eye, the level of homogeneity with regard to intensity may not be relevant. All that is necessary is to provide a population that is sufficiently homogeneous to be seen as red, or a population that is sufficiently homogeneous to be seen as yellow or green or blue as the case may be. On the other hand, if the authentication requires the generation of complex levels of detection which require particular intensities or specific wavelengths of emission, the populations may need to reach higher levels of homogeneity, possibly as high as that wherein at least 90-99% of the particles in the population have the same absorption maximum and possibly do not vary in intensity by more than 1 or 2%. Depending on usage, the variability may be greater.

[0074] The "prescribed form" of the authentication system refers to the particular population or mixtures of populations of diamond particles that are used in a particular authentication system with respect to a particular product. The product to be analyzed will either have the prescribed form contained within it, in which case it is indeed authentic, or it will have no authentication system or a different authentication system in which case it is not authentic. The product or packaging to be tested will be tested for this prescribed form, and it may or may not in fact contain it.

[0075] The prescribed form is typically designed by the manufacturer or by a supplier and under the control of the designer. Because the authentication systems consist entirely of inert diamond material regardless of the proportions of any of the various populations in the prescribed form,, the designer is at liberty to select from a multitude of possible variations.

[0076] As used herein, "product" or "substrate" refers to the material which is to be

authenticated. Thus, whether the product or substrate is a tablet, a piece of cloth, a solid article, a powder or a liquid composition, an emulsion or a semisolid, an appropriate authentication method employing the diamond particles of the invention can be designed. "Product" also includes packaging, as well as intermediates which are to be converted to product. For example, if the product is a finished pharmaceutical dosage, the active pharmaceutical ingredient (API) may be labeled. Any intermediate that is carried over to the final product can be labeled.

[0077] The authentication of the labeled product involves detecting spectral data from a tested product and comparing these data to the corresponding data in the authentication system for that product. The determination of these data and the comparison may be performed simultaneously in the same apparatus or separately in the same apparatus or in two different instruments that may be in the same or different locations. Thus an apparatus may be programmed to interact with the product based on predetermined parameters and register a match or no match. The components which interact with the product for spectral data determination and which make the comparison may thus be the same or different in the same apparatus. However, these functions may be entirely separate and done by two different instruments and the different instruments may or may not be at the same physical site, since the spectral data can be transmitted, optionally in encrypted form, to an interrogation device at a remote location. A "tagged" product refers to a product which has been labeled with diamond particles.

[0078] While very important products as subjects for the authentication method of the invention are pharmaceutical compositions, including those for oral administration as well as alternative formulations such as biologicals or parenteral formulations, a wide variety of products can be authenticated using this labeling system. This is important, for example, in connection with luxury goods where verification of point of origin is critical to prevent piracy. Illustrative goods include cosmetics, fragrances, clothing, accessories such as wallets or purses, and the like. Inclusion in ink used to identify the packaging of goods as trademarked is also important and both the trademark itself and the trademarked product can be similarly labeled or labeled with different compositions of the invention. Other important substrates include documents, currency, stamps, tax stamps, inks in general, and any product where either the origin of manufacture or other index of authenticity is important. In some instances, especially where there is a known problem of undercutting regulated products so as to undermine their safety, authenticating products such as foods by the invention method is a solution to the problem. Textiles, paints, mechanical parts and documents of value, such as stock certificates and monetary instruments may be labeled according to the invention.

[0079] One particularly useful embodiment relates to "solid oral dosage forms" or SODF's for which the FDA has issued guidelines for authentication using physical-chemical identifiers.

SODF's include without limitation, tablets, capsules containing powders, gels and the like.

[0080] As used herein, articles such as "a", "an" and the like are generally used to mean either one or more than one unless otherwise indicated. Further, where ranges of parameters are disclosed, where the ranges include integers, all integers within the cited range are included as if specifically set forth. For example, a range of variation of 4-10 possible intensities would specifically include variations that include 5, 6, 7, 8 or 9 different intensities. This stipulation is in order to avoid repetitious explicit enumeration and make the present specification more readable.

[0081] The homogeneity of individual populations can be assured by preparing diamond particles according to methods known in the art that generate specific color centers that are associated with particular spectra by controlling the conditions so as to result in a homogeneous population. The number of such color centers will determine the intensity of fluorescence. The homogeneity of the populations can also be assured by separating mixtures of diamond particles into homogeneous groups, for example, by flow cytometry. It has been shown that commercially available diamond particles can indeed be separated into individual color populations by this method. Thus, populations that are sufficiently homogeneous for a particular method can be obtained using standard techniques.

[0082] Homogeneous populations are particularly useful in preparing controlled authentication systems where visible color is used by the purchaser to authenticate the product on site by using a specific excitation wavelength and observing a defined color. For these systems, it is typical to use a combination of at least two populations, or more— three populations, four populations, five populations, etc., depending on the number of colors that the user is asked to observe. If only a single color is to be observed, then the particles may be distributed throughout the product, for example, if the product is a foodstuff or a pill, the user can be instructed to employ a particular excitation wavelength and instructed to expect to see, for example, red or yellow or blue. However, if a combination of colors is expected, it may be desirable to distribute the particles in a pattern on the surface so that the particles that emit, for example, green, can be readily distinguished from those that emit red. This is not always necessary since more than one color seen together will provide a different hue— e.g., red and blue looks purple. These combinations may also take advantage of differing intensities and/or durations of emission in the populations, but this determination is generally more complex since determination of intensity and duration levels with the naked eye is difficult, especially discerning among a reasonably large number of such levels. It is contemplated that, for example, intensity levels differing over a range where 5 or 7 or 10 intensity levels could be specified, but would require detection devices. However, the user could verify his initial authentication by obtaining an emission profile of the authentication system and sending it electronically to a data center that is able to display and match the relevant spectral data with those of the product. Alternatively, this could be done on site using an appropriate

interrogation device.

[0083] It should also be noted that visual appearance from a combination of homogeneous populations may not be intuitive. For example, as shown below, a 1 : 1 : 1 mixture of red:green:blue particles appears yellow.

[0084] Thus, for homogeneous populations, in one very simple embodiment, a single population of diamond particles may be used. To use a pharmaceutical dosage form as an example, the authenticity of the composition can be verified by the end-user by illuminating the formulation with the appropriate wavelength and discerning the presence or absence of the expected emission color simply by visual detection. A simple emission spectrum may be obtained using a spectrophotometer. If desired, this can also be authenticated by a more complex readout of the spectrum including, optionally, the identification of the zero phonon line (ZPL) which represents pure excitation absent variation due to alteration in vibrational states and by measuring duration. The existence of a ZPL is emblematic of diamond and its measurement can be used to confirm the presumed presence of this material.

[0085] For straightforward detection without any sophisticated measurement of spectra, a number of devices are readily available. As noted above, an LED light that emits 360 nm is commonly available and this is capable of excitation of emission in the visible range of varying colors depending on the nature of the particles themselves. In addition, for a modest cost, devices are available that permit different excitation wavelengths to be employed as displayed by the device and the corresponding emission wavelength(s) can be displayed numerically or would be visible to the naked eye.

[0086] Devices are available that also detect emissions in the infrared and can detect levels of intensity. Raman spectroscopy may be used to detect low frequency modes.

[0087] While the system described in the previous paragraphs is effective per se, it is advantageous to use a more complex authentication system in order to provide a specific authentication for a particular batch or a particular type of dosage. By employing more than one population with varying, for example, just the emission/excitation wavelength combinations and intensities, a very large number of distinctive patterns can be generated.

[0088] For example, using 4 colors and 10 intensity levels, many thousands of different patterns can be obtained. Adding duration of the emission as a variable results in even more possibilities.

[0089] If even more colors are used or more intensities are used, the number would be even higher. Thus, a large number of combinations can be prepared to distinguish individual batches or individual formulations. There would be a sufficient number of individual signatures thus, to permit the identification of individual batches, for example, of a pharmaceutical dosage not just to verify the nature of the drug itself. Even larger numbers of alternatives can be prepared by varying among more colors or including more different levels of duration and/or intensity.

[0090] In some embodiments, it is advantageous to use a heterogeneous population of particles so that complex emissions are obtained. Populations with random assortments of particles with varying numbers of color centers and varying types of colors centers can be obtained, and can occur in nature. These have inherently high flexibility. For a random heterogeneous population, unique emissions would be generated, by irradiation with light of sufficient wavelength to excite various color centers in the random mixture at various intensities and durations. This embodiment works best with respect to obtaining data on site which is electronically transmitted to a matching facility to permit authentication; however, if facilities or a programmable detector incorporating interrogation device are available, on-site determination may also be practical. Alternatively, the product could be sent off site for authentication.

[0091] A particularly useful combination is that of an unseparated mixture of diamond particles as a fraction of the total label where the remainder of the label consists of one or more

homogeneous populations of the separated forms. The individual separated forms generate discrete emission peaks, while the unseparated mixture is relatively silent in terms of visible emission but has a characteristic infrared spectrum.

[0092] Thus, an extra level of authentication can be provided by adding to the known ratios of components a portion which constitutes unseparated diamonds. These mixtures appear black to the naked eye and also generate an essentially null spectrum as described in Figure 9 in Example 5 below. However, as shown in Figure 8, also in Example 5, this mixture provides a characteristic infrared spectrum that is excitable by visible light. This aspect of authentication is more difficult to counterfeit as mixtures, for example, of various dyes would not have this result. This unseparated mixture of diamond particles can be used alone or added as a portion of the label and superimposed upon the remaining separated components.

[0093] In that regard, by mixing various proportions of red, blue and green diamond particles, dosages or labeled substrates can be obtained that appear yellow to the naked eye but when examined spectroscopically clearly show the ratios of components. This is illustrated in Example 6 below. It appears that several dozen different spectroscopically distinguishable but visually indistinguishable yellow substrates may be obtained by varying proportions of these three components.

[0094] Another dimension of authentication can be obtained by adding to the substrate a hygroscopic organic component that becomes dehydrated upon application of pressure. This is particularly useful in the context of orally administered tablets because a particular hygroscopic organic material— magnesium stearate— is a common component of such dosage forms. This particular hygroscopic hydrophobic compound has the property of causing an indigo-violet shift in the spectrum known as a leafing effect. This leafing effect results also in a separation of diamond particles distributed between the magnesium stearate and the remainder of a hydrophilic substrate. When separated diamond particles according to color are included in substrates which contain the hygroscopic organic material and then subjected to pressure, for example, in making a tablet, the hygroscopic material is at least partially dehydrated resulting in what to the resident diamond particles appears to be a two-phase system. The substrate, for example tablets, then assumes a speckled appearance due to the uneven distribution of the diamond particles. This, too, is difficult to duplicate in a counterfeit material since typically only diamond particles exhibit this property of uneven distribution among the organic/hydrophobic, now dehydrated material and the remainder of more hydrophilic materials included in the substrate. Counterfeited substrates that substitute other fluorescent substances for diamond particles do not have this property.

[0095] The levels of particles required to result in successful detection depend to some extent on the method of measurement. It appears that to detect the presence of one or more colors of taggant visually, levels only of approximately 10-100 ppm, i.e., 0.001% - 0.01% by weight, are required; or even 1 ppm or 0.0001%) as a lower limit. However, very simple and commercially available instrumentation can easily detect 50-100 ppb. The lowest limit needed for detection depends on the sophistication of the detector and thus considerably lower levels could also be detected with the appropriate equipment.

[0096] Particularly where complex mixtures of diamond particles are employed, a more sophisticated system for identification is helpful. As noted above, a reasonably simple tagging method can be verified simply using a handheld LED device which permits visual inspection. Generation of a simple spectrum will also enable direct observation and evaluation of the spectrum itself, e.g., as printed out over a suitable wavelength range. On the other hand, especially but not necessarily where complex mixtures, rather than, for example, a particular design on the surface of a solid formulation are used, a programmed detector incorporating an interrogation device is often employed. Thus, the intensity and/or wavelength and/or duration of the various peaks or a selected portion thereof in the emission spectra of the particular combination of populations of diamond particles combined with the appropriate excitation parameters can be recorded in such a detector which can then either accept or reject authentication based on matching or non-matching of the embedded information with that generated by a physically obtained emission spectrum or portion thereof of the product or its labeling. These data may be assigned a code associated with the product which may be secret known to an authentication service provider.

[0097] One illustrative but not limiting embodiment of the overall system as applied to an oral dosage form is shown in Figure 16. In this exemplified procedure, a mixture of four populations of diamond particles is used— red (R), green (G), blue (B) and infrared (IR)— and mixed in various ratios. A particular mixture is illustrated in the figure. The composition of the mixture can be determined by the dosage manufacturer or a supplier. The mixture of specified proportions is then characterized in terms of its spectral characteristics and added either, in this case, to the active pharmaceutical ingredient (API) or to a batch used to prepare the finished product. In each case, spectral data are recorded from the API, batch or finished product and assigned a suitable code. It is preferable that the authentic spectral data for the product to be obtained from the product itself since the chemical and/or physical form of the product may influence these somewhat. Authentic spectral data from various products are encrypted for data storage and are programmed in advance into an interrogation device through a USB or other suitable connection. The interrogation device may be part of (as shown in Figure 16) or may be separate from a detector for spectral data of the product to be tested in which case data from a detector are fed to the interrogation device. The interrogation device then attempts to match the authentic spectral data with spectral data obtained from the product(s) tested by comparing them. The detector shown in Figure 16 (or the

interrogation device in general) may be housed in a handheld apparatus, but need not be and may be remotely programmable, but need not be. (It is often more convenient to employ handheld remotely programmable devices, but this is not a necessity.) The match or non-match is then read — where there is a match, the tested product is considered authentic whereas if there is no match it is considered counterfeit.

[0098] Detectors of the type that can be configured to be programmable to match incoming spectra from programmed-in spectra are described in U.S. patent documents 2003/0173539;

2004/0169847; 2011/0090485 and 2013/0277576. In some cases, only predetermined spectral data are programmed for determination into the device.

[0099] The number of spectral parameters to be measured is dependent on the complexity built into the assay system. The possible parameters include the wavelength, intensity, and duration of the peaks in the excitation and emission spectra. However, it is not necessary in every case to measure each and every one of these parameters. It may be sufficient to measure only a subset, such as a combination of wavelength and intensity of the emission spectrum pattern holding the excitation energy constant. Alternatively, the excitation energy or intensity can be varied and a simpler form of the emission spectrum measured. The design of the levels of the various parameters available is well within the skill of the ordinary artisan familiar with the spectral patterns emitted by materials in general. Additionally, another level of sophistication may be added by incorporating detection of magnetic properties via spectroscopic or non-spectroscopic methods known to one skilled in the art. These methods of detecting magnetic properties include electron paramagnetic resonance (EPR) spectroscopy (also known as electron spin resonance (ESR) spectroscopy). In another embodiment, diamond particles with no color centers, are isolated.

These particles have a distinct raman shift and absorbance as compared to diamond particles with color centers that possess optical characteristics. In another embodiment, the use of ¹³C MR is used to determine the purity of the diamond particles. The chemical shift (i.e a single peak at 38 PPM) is not influenced by the use of other materials.

[00100] The system shown in Figure 16 is only one of a number of possibilities. Various types of detectors can be used with various capabilities and the nature of the authenticating entity (e.g., the end user or a service provider) is variable depending on the design of the business arrangements associated with the technology.

[00101] In addition to tagging dosage forms or other products with the diamond particles, packaging for a product may be similarly tagged with the diamond particles corresponding to the taggant used in the product. Thus, an easy way to detect counterfeiting of the product would comprise labeling both the product and the packaging for the product with the same coded mixture of diamond particles wherein a discrepancy between the packaging and the product would indicate tampering. The packaging label is a useful substitute for package labeling that currently may embody a barcode. The necessity for the barcode is obviated by replacing it with the diamond particle taggant mixture included in the ink. The same prescribed form of diamond particles could be included both in the product itself and in the ink used to label the packaging. This is the most convenient arrangement, but clearly not the only possibility— each could be independently labeled and assessed accordingly.

[00102] All documents noted herein are incorporated by reference as if fully set forth.

5.3.1. "DANCING DIAMONDS"

[00103] Another method of encryption and authentication involves "dancing diamonds," wherein the population of diamond particles appears to move when exposed to varying excitation wavelengths. Since different populations are excited by different wavelengths of light and emit light at specific wavelengths, by varying excitation wavelengths over a protracted interval, and detecting the emissions, substrates containing mixtures of homogenous populations of diamond particles can appear to contain a "population" that moves. In this method, homogeneous populations may be required, as an interference phenomenon generally exhibited by diamond particles in heterogeneous populations may result in a black appearance.

5.3.2. COMBINATION WITH OTHER CHEMICAL AUTHENTICATION

METHODS

[00104] Systems involving photo-luminescent materials (phosphors) have been used as a covert method of product authentication. Up converting phosphors convert lower energy light to higher energy light, for example, when irradiated with low energy infrared (IR) light, the up converting phosphor emits higher energy visible light. Down converting phosphors convert higher energy light to lower energy light, for example, when irradiated with high energy X-rays, the down converting phosphor emits lower energy visible light. Up converting or down converting phosphors can be combined with diamond indicia (either a homogenous population, mixtures thereof, a heterogeneous population or a mixture of a homogenous and heterogeneous population) to add an additional covert method of authentication.

[00105] Another embodiment relates to using the diamond particles in combination with another or other nontoxic materials. The other materials are those that convert, absorb, reflect, or shift electromagnetic radiation from one wavelength to another wavelength. The material or materials do not interfere with detection of the diamond particles and are used in conjunction with signal interpretation of the final compositions. The detection scheme includes single signal processing or heterodyne detection. An example is as follows: A pharmaceutical dosage form formulated using methods known in the art is formulated to contain 50 ppm diamond nanoparticles in three different ratios in combination with an up conversion or "anti-stokes" pigment such as a gadolinium chelate (UC-2; Honeywell corporation) generally at a concentration of between 0.01% and 45.0%. The resulting composition is interrogated utilizing excitation at single or dual wavelengths. The signals related to the quantum efficiency of the diamond nanoparticles and the pigment are compared. The emission lifetime(s) of the material or materials and the diamond particles may also be detected. The combination of diamond and the other material or materials can be mathematically matched to a standard stored spectrum and a handheld detector can determine the presence of both or either material.

[00106] In another embodiment, diamond particles are used in combination with printed layers of high depolarizing (i.e calcium carbonate) and highly polarizing (i.e. titanium oxide) materials. The final effect is an invisible print or coating that reveals an image through an optical film that allows the passage of visible light in only one plane polarized direction.

5.3.3. COMBINATION WITH COLOR-SHIFTING INK

[00107] Color-shifting inks have been used as an overt method of product authentication. In this method, special pigments which change color upon viewing at different angles are incorporated into an ink. As described herein, the tagging of inks with diamond particles can be used as part of an authentication system. Employing color-shifting inks tagged with diamond particles can add a layer of overt detection to the diamond particle based authentication system.

[00108] In another embodiment, diamond particles are combined with nontoxic materials to cause a visual change of color that is angle dependent such as a color-shifting pigment, dye or liquid crystal. The diamond is machine read and the color shift material is used for a first-level visual method to authenticate. Examples of nontoxic angle dependent pigments are pearlescent pigments manufactured by Merck Co., or lake pearlescent pigments manufactured by Colorcon. These pigments can be combined with nontoxic D&C and/or FD&C visible dyes that contain "spectral notches" to allow for the creation of a further shifting effect.

5.4. AUTHENTICATED PHARMACEUTICALS

[00109] In one embodiment, the authenticated pharmaceutical product comprises an active pharmaceutical ingredient (API) and diamond particles. The diamonds can be compounded or formulated with the API or applied to the compounded product as a coating. In another embodiment, the active pharmaceutical ingredient (API) is selected from the list of drugs disclosed in the Physician's Desk Reference (69^th Ed.; PDR Network, LLC; Montvale, NJ; 2015), which is incorporated herein by reference.

[00110] In one embodiment, the active pharmaceutical ingredient (API) is abacavir, abacavir sulfate, abatacept, abiraterone acetate, acerola cherry, acetaminophen, acetohydroxamic acid, acitretin, aconitum napellus, adalimumab, adapalene, albiglutide, albuterol, albuterol sulfate, alendronate sodium, A-lipoicum acidum, aliskiren, allium cepa, alogliptin, alpha carotene, alpha lipoic acid, alpha tocopherol acetate, ambriesentan, aminobenzoate potassium, aminohippurate sodium, aminosalicylic acid, 4-amino-salicylic acid, 5-amino-salicylic acid, amlodipine, amoxicillin, amphetamine, anthocyanidins, apixaban, aprepitant, arabinogalactan, arformoterol tartrate, argatroban, aripiprazole, armodafinil, arnica Montana (radix), artemether, ascorbic acid, ascorbyl palmitate, asenapine, atazanavir, atomoxetine, atorvastatin, atovaquone, atropine sulfate, azelaic acid, azelastine HCl or aztreonam.

[00111] In another embodiment, the active pharmaceutical ingredient (API) is basiliximab, beclomethasone dipropionate monohydrate, belatacept, belimumab, belladonna, bellis perennis, bendamustine HCl, benzoyl peroxide, beractant, berbenne, besifloxacin, beta-carotene, beta-glucan, betaine hydrochloride, betamethasone acetate, betamethasone dipropionate, betamethasone sodium phosphate, beta-tocopherol, bevacizumab, bifidobacterium breve br 03, bifidobacterium lactis bs 01, bioblavonoids, bimatoprost, biotin, bisacodyl, boceprevir, boron, boron ascorbate, boron citrate, bortezomib, boswellia extract, brassica oleracea, brimonidine tartrate, bromelain, bromocriptine mesylate, brinzolamide, budesonide, buprenorphine, buprenorphine hydrochloride or bupropion hydrochloride.

[00112] In another embodiment, the active pharmaceutical ingredient (API) is calciprotriene, calcium ascorbate, calcium carbonate, calcium chloride, calcium citrate, calcium folinate, calcium fumarate, calcium malate, calcium pantothenate, calcium succinate, calendula officinalis, camellia sinensis, camphor, canagliflozin, canakinumab, capecitabine, capsicum annuum, carbidopa, carbohydrates, carfilzomib, cartilago suis, carvedilol, carvedilol phosphate, caspofungin acetate, catechins, cefuroxime axetil, celecoxib, ceritinib, certolizumab pegol cetuximab, chamomilla, cherry extract, chlorophyll, chloroxylenol, cholecalciferol, choline bitartrate, chorionic

gonadotropin, chromium, chromium ascorbate, chromium picolinate, chromium polynicotinate, chrysanthemum morifolium, cilastatin, cinacalcet, cinnamon, ciprofloxacin HCl, cistracurium besylate, citrate, citrus bioflavonoids, citrus sinensis, clarithromycin, clavulanate potassium, clindamycin phosphate, clopidogrel, clozapine, cobicistat, coenzyme A, coenzyme Q-10, colchicine, colesevelam HCl, collagenase, colostrums, conjugated estrogens, copper, copper gluconate, cordyceps sinensis mushroom extract, cornsilk, crocus sativus, crofelemer, cupric oxide, cyanocobalamin, cyclosporine or cysteine.

[00113] In another embodiment, the active pharmaceutical ingredient (API) is dabrafenib, D- alpha tocopherol, D-alpha tocopheryl succinate, dabigatran etexilate mesylate, dapsone,

daptomycin, darbepoetin alpha, darunavir, dasatinib, D-calcium pantothenate, deferasirox, delavirdine mesylate, delta-tocopherol, denosumab, desloratadine, desvenlafaxine succinate, dexamethasone, dexlansoprazole, dexmethylphenidate hydrochloride, dextroamphetamine, DHA (docosahexaenoic acid), dibasic sodium phosphate, diclofenac sodium, dietary supplement, difluprednate, digestive enzymes, dimethyl fumarate, dioctyl sodium sulfosuccinate, diphtheria & tetanus toxoids and acellular pertussis vaccine adsorbed, diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, diphtheria and tetanus toxoids and acellular adsorbed (hepatitis B (recombinant) and inactivated poliovirus vaccine), dipotassium phosphate, dipyridamole, divalproex sodium, DL-alpha tocopheryl acetate, docosahexaenoic acid (DHA), docusate sodium, dolutegravir, dorzolamide hydrochloride, doxycycline, D-ribose, dronedarone, drospirenone, dulcamara, duloxetine, duloxetine HC1 or dutasteride.

[00114] In another embodiment, the active pharmaceutical ingredient (API) is Echinacea, enchincea purpurea, efavirenz, eicosapentaenoic acid (EPA), elecampane root extract, eletriptan hydrobromide, eltrombopag, elvitegravir, embryo totalis suis, emtricitabine, entecavir, enzymes (collagenolytic), enzymes (debridement), enzymes (digestive), epinephrine, epoetin alpha, epoprostenol sodium, eptifibatide, erlotinib, ertapenem, escitalopram, eslicarbazepine acetate, esomeprazole magnesium, estradiol, eszopiclone, etanercept, ethinyl estradiol, etonogestrel, everolimus, exenatide, ezetimibe or ezogabine.

[00115] In another embodiment, the active pharmaceutical ingredient (API) is fatty acids, febuxostat, fennel, fenofibrate, fenofibric acid, fentanyl, ferrous fumarate, ferrous gluconate, fertilized avian egg extract, fiber, fiber (dietary), filgrastim, finasteride, fingolimod, flibanserin, fluoxetine, fluticosone furoate, fluticasone propionate, folate, folic acid, follitropin beta, formaldehyde, formoterol fumarate, formoterol fumarate dihydrate, fosamprenavir calcium, fosaprepitant dimeglumine, fumarate or funiculus umbilicalis suis.

[00116] In another embodiment, the active pharmaceutical ingredient (API) is galunisertib, gamma tocopherol, ganirelix acetate, ganoderma lucidum mushroom extract, ginger, glatiramer acetate, glimepiride, glucosamine hydrochloride, glycerin, glyceryl trinitrate, grape seed extract, green tea extract or guanfacine.

[00117] In another embodiment, the active pharmaceutical ingredient (API) is haemophilus B conjugate vaccine (meningococcal protein conjugate), haemophilus B conjugate (meningococcal protein conjugate) and hepatitis B (recombinant) vaccine, hamamelis virginiana, hawthorn berry extract, hemin, hepar sulphuris calcareum, hepatitis A vaccine, hepatitis A vaccine (inactivated), hepatitis A & hepatitis B (recombinant) vaccine, hepatitis B vaccine (recombinant), hesperidin, hexacosanol, human papillomavirus bivalent (types 16 and 18) vaccine (recombinant), human papillomavirus quadrivalent (types 6, 1 1, 16, and 18) vaccine (recombinant), hyaluronidase human, hydrochlorothiazide, hydrocodone bitartrate, hydromorphone hydrochloride, hydroxocobalamin, hyoscine hydrobromide, hyoscyamine sulfate or hypericum perforatum. [00118] In another embodiment, the active pharmaceutical ingredient (API) is ibuprofen, ibuprofen lysine, idelalisib, iloperidone, imatinib mesylate, imipenem, indacaterol, indinavir sulfate, infliximab, influenza vaccine, inland sea trace minerals, inositol, insulin (human (RDNA origin)), insulin aspart (RDNA origin), insulin aspart protamine (RDNA origin), insulin detemir (RDNA origin), insulin glargine, insulin lispro, insulin lispro protamine, interferon alfa-2B, interferon beta-la, interferon beta-lb, recombinant, iodine, ipilimumab, ipratropium bromide, iron, iron carbonyl, isotretinoin or ivermectin.

[00119] In another embodiment, the active pharmaceutical ingredient (API) is kelp or krill oil.

[00120] In another embodiment, the active pharmaceutical ingredient (API) is lacosamide, lactobacillus acidophilus LA 02, lactobacillus rhamnosus LR 04, lactoferrin, lamivudine, lamotrigine, lansoprazole, lapatinib, L-arginine, L-ascorbates, L-aspartic acid, L-carnitine, L- citrulline, L-cysteine, letrozole, leuprolide acetate, levalbuterol tartrate, levocarnitine, levodopa, levomefolate, levothyroxine sodium, lidocaine, linaclotide, linagliptin, linezolid, lipoic acid, liraglutide (RDNA origin), lisdexamfetamine dimesylate, lisinopril, L-lysine, lopinavir, loteprednol etabonate, lovastatin, loxapine, L-proline, L-selenomethionine, lubiprostone, lumefantrine, lurasidone hydrochloride, lutein or lycopene.

[00121] In another embodiment, the active pharmaceutical ingredient (API) is magnesium, magnesium amino acid chelate, magnesium ascorbate, magnesium citrate, magnesium hydroxide, magnesium oxide, magnesium sulfate, malate, manganese, manganese ascorbate, manganese gluconate, mannitol, maraviroc, marine protein, maritime pine extract, measles mumps and rubella virus vaccine live, measles mumps rubella and varicella virus vaccine live, medroxyprogesterone, memantine HCl, menaquinone, meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine, menthol, mercurius solubilis, meriva bioavailable curcumin complex, mesalamine, metformin, metformin hydrochloride, methylcobalamin, methylnaltrexone bromide, methylphenidate, metoprolol succinate, milk of magnesia, millefolium, milnacipran HCl, mineral oil, mirabegron, mirtazapine, modafinil, molybdenum, molybdenum ascorbate, molybdenum citrate, mometasone furoate, mometasone furoate monohydrate, monobasic sodium phosphate, montelukast sodium, moxifloxacin hydrochloride, multiminerals, multivitamins with minerals, mupirocin, mupirocin calcium, mushroom mycelia or mycophenolic acid.

[00122] In another embodiment, the active pharmaceutical ingredient (API) is N-acetylcysteine, nadidum, naloxone hydrochloride, naltrexone hydrochloride, nanofactor, naratriptan

hydrochloride, natalizumab, natrum oxalaceticum, natural vanilla, nebivolol, nelarabine, nepafenac, niacin, niacinamide, niacinamide ascorbate, nicotinic acid, nigella sativa, nilotinib, nitroglycerin, nivolumab, nopalea sonoran bloom proprietary blend, norelgestromin, norethindrone acetate or norgestimate.

[00123] In another embodiment, the active pharmaceutical ingredient (API) is octacosanol, octreotide acetate, ofatumumab, olive extract, olive oil, olmesartan medoxomil, olopatadine HCl, omalizumab, omega-3 fatty acids, omega-3-acid ethyl esters, omega-3 polyunsaturates, omeprazole, ometasone furoate monohydrate, ondansetron, ondansetron hydrochloride, onion, OPC, opuntia ficus-indica, oritavancin, oseltamivir phosphate, oxcarbazepine, oxycodone hydrochloride or oxymorphone HCl.

[00124] In another embodiment, the active pharmaceutical ingredient (API) is paliperidone palmitate, palivizumab, panax ginseng, pancrelipase, pantothenate calcium, pantothenic acid, papilloma virus quadravalent vaccine, para-aminobenzoic acid, paricalcitol, pazopanib, PEG-3350, pegfilgrastim, peginterferon alfa-2B, pembrolizumab, pemetrexed disodium, phenobarbital, phenytoin, phosphorus, phylloquinone, phyto protein, phytosterols, pine bark extract, pioglitazone, pitavastatin, pitcher plant distillate, placenta suis, pneumococcal 13-valent conjugated vaccine, pneumococcal vaccine polyvalent, policosanol, polygonatum multiflorum, pomegranate fruit extract, pomegranate juice powder, posaconazaole, potassium, potassium ascorbate, potassium chloride, potassium citrate, potassium iodide, potassium sulfate, prasugrel, pregabalin,

progesterone, proguanil hydrochloride, propafenone hydrochloride, protein-bound paclitaxel, protein preparations, prunus cerasus, pseudoephedrine sulfate, psyllium preparations, punica granatum, pyridoxal 5 '-phosphate or pyridoxine hydrochloride.

[00125] In another embodiment, the active pharmaceutical ingredient (API) is quercetin, quercetin dehydrate or quetiapine fumarate.

[00126] In another embodiment, the active pharmaceutical ingredient (API) is rabeprazole sodium, radium RA 223 dichloride, raloxifene HCl, raltegravir, ranibizumab, ranitidine, ranitidine hydrochloride, ranolazine, raxibacumab, red wine extract, regorafenib, resveratrol, retapamulin, retinyl palmitate, rhubarb, rhus toxicodendron, ribavirin, riboflavin, riboflavin 5' phosphate, rifaximin, rilpivirine, risedronate sodium, ritonavir, rituximab, rivaroxaban, rivastigmine, rocuronium bromide, roflumilast, ropinirole, rosiglitazone maleate, rosuvastatin, rosuvastatin calcium, rotavirus vaccine (live, oral), rotavirus vaccine (live, oral, pentavalent), rutin or ruxolitinib. [00127] In another embodiment, the active pharmaceutical ingredient (API) is salmeterol, salmeterol xinafoate, salmon oil, sanguinaria canadensis, sarraceniaceae, saxagliptin, scopolamine hydrobromide, selenium, selenium amino acid complex, senna, sevelamer carbonate, sevoflurane, short ragweed pollen allergen extract, sildenafil, sildenafil citrate, silicon amino acid complex, silodocin, simeprevir, simethicone, simvastatin, sitagliptin, (6S)-5-methyltetrahydrofolate, sofosbuvir, sodium, sodium ascorbate, sodium bicarbonate, sodium chloride, sodium fluoride, sodium oxybate, sodium sulfate, sofosbuvir, solifenacin succinate, somatostatin analogue, somatropin (RDNA origin), sorafenib, soy oil, succimer, succinate, sucralfate, sulphur, sumatriptan, sumatriptan succinate or Symphytum officinale.

[00128] In another embodiment, the active pharmaceutical ingredient (API) is tacrolimus, tadalafil, tafluprost, tamsulosin hydrochloride, tapentadol, tasimelteon, taurine, tazarotene, telaprevir, telmisarten, temozolomide, tenofovir disoproxil fumarate, testosterone, tetanus toxoid (reduced diphtheria toxoid and acellular pertussis vaccine, adsorbed), tetracosanol, theobroma cacao, thiamine, thiamine hydrochloride, thyroid, ticagrelor, ticarcillin disodium, timolol maleate, timothy grass pollen allergen extract, tinidazole, tiopronin, tiotropium bromide, tobramycin, tocopherols, tocotrienols, tofacitinib, tolterodine tartrate, tolvaptan, topiramate, topotecan, topotecan hydrochloride, trametinib, trandolapril, transfer factor, trastuzumab, travoprost, tretinoin, triacontanol, trimterene, turmeric or turmeric extract.

[00129] In another embodiment, the active pharmaceutical ingredient (API) is umeclidinium, undaria pinnatifida, undecylenic acid, undenatured type II collagen, unicity 7X or ustekinumab.

[00130] In another embodiment, the active pharmaceutical ingredient (API) is valacyclovir hydrochloride, valproic acid, valsartan, vanadium, vanadium ascorbate, vanadium citrate, vardenafil HCl, varenicline, varicella virus vaccine live, vegetable blend, vegetable fiber, verapamil hydrochloride, vilanterol, vilazodone HCl, vitamin A, vitamin B₃, vitamin B₆, vitamin B_i2, vitamin C, vitamin D, vitamin D₃, vitamin E, vitamin K, vitamins with minerals, vitis vinifera, vorapaxar, vorinostat or vortioxetine.

[00131] In another embodiment, the active pharmaceutical ingredient (API) is warfarin sodium, water (purified) or whey protein.

[00132] In another embodiment, the active pharmaceutical ingredient (API) is xylitol.

[00133] In another embodiment, the active pharmaceutical ingredient (API) is zanamivir, zeaxathin, zidovudine, zinc, zinc ascorbate, zinc citrate, zinc oxide, zinc picolinate, zinc sulfate, zoledronic acid, Zolpidem tartrate, zoster vaccine live or zostavax vaccine live. [00134] In another embodiment, the active pharmaceutical ingredient is a pharmaceutically acceptable salt, free form or a salt thereof, clathrate, solvate, tautomer, isotopologue, prodrug, or stereoisomer of any of the foregoing. In another embodiment the authenticated pharmaceutical product comprises two or more active pharmaceutical ingredients.

[00135] In one embodiment, the active pharmaceutical ingredient is selected from Table 2. In another embodiment, the route of administration of the authenticated pharmaceutical product comprising the active pharmaceutical ingredient is selected from, but not limited to, oral

(gastrointestinal), injection (parenteral, subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal), mucosal, topical/dermal (transdermal, buccal), or inhalation.

[00136] In a preferred embodiment, the route of administration of the authenticated pharmaceutical product corresponding to the active pharmaceutical ingredient listed in the left column of Table 2, is listed in the right column of Table 2.

[00137] Table 2.

Epoetin alpha Injection

Erlotinib Oral

Escitalopram Oral

Esomeprazole magnesium Oral

Eszopiclone Oral

Etanercept Injection

Everolimus Oral

Ezetimibe Oral

Filgrastim Injection

Fingolimod Oral

Fluticasone propionate Inhalation

Glatiramer acetate Injection

Imatinib mesylate Oral

Infliximab Injection

Insulin aspart Injection

Insulin detemir Injection

Insulin glargine Injection

Insulin lispro Injection

Interferon β-la Injection

Interferon β-1 b Injection

Levothyroxine sodium Oral

Linezolid Oral and injection

Liraglutide Injection

Lisdexmfetamine dimescylate Oral

Lurasidone HCI Oral

Memantine HCI Oral

Modafinil Oral

Natalizumab Injection

Nebivolol Oral

Nivolumab Injection

Octreotide acetate Injection

Olmesartan medoxomil Oral

Omalizumab Injection

Ometasone furoate monohydrate Inhalation

Oxycodone HCI Oral

Paliperidone palmitate Injection

Palivizumab Injection

Papilloma virus quadravalent vaccine Injection

Pegfilgrastim Injection

Pembrolizumab Injection

Pemetrexed disodium Injection

Pneumococcal 13-valent conjugated vaccine Injection

Pregabalin Oral

Protein-bound paclitaxel Injection

Quetiapine fumarate Oral

Raloxifene HCI Oral

Raltegravir Oral

Ranibizumab Injection

Rituximab Injection

Rivaroxaban Oral Rosuvastatin calcium Oral

Sevelamer carbonate Oral

Sildenafil Oral

Simeprevir Oral

Simvastatin Oral

Sitagliptin Oral

Sofosbuvir Oral

Solifenacin succinate Oral

Tadalafil Oral

Tiotropium bromide Inhalation

Trastuzumab Injection

Ustekinumab Injection

Valsartan Oral

Zoster vaccine - live Injection

Budesonide + formeterol fumerate dihydrate Inhalation

Buprenorphine HCI + naloxone HCI Mucosal

Efavirenz + emtricitabine + tenofovir disoproxil

fumarate Oral

Elvitegravir + cobicistat + emtricitabine +

tenofovir disoproxil fumarate Oral

Emtricitabine + rilpivirine + tenofovir disoproxil

fumarate Oral

Emtricitabine + tenofovir disoproxil fumarate Oral

Ezetimibe + simvastatin Oral

Fluticasone propionate + salmeterol Inhalation

Ipratropium bromide + albuterol Inhalation

Olmesartan medoxomil + hydrochlorothiazide Oral

Sitagliptin + metformin HCI Oral

[00138] In one embodiment, the authenticated pharmaceutical product comprises an active pharmaceutical ingredient approved by the United States FDA for treating or preventing a disease, disorder, illness, medical condition, morbidity, or syndrome in a subject. In certain embodiments, the disease, disorder, illness, medical condition, morbidity, or syndrome is bacterial infections and mycoses, cardiovascular diseases, chemically-induced disorders, congenital, hereditary, and neonatal diseases and abnormalities, dental conditions, digestive system diseases, disorders of environmental origin, endrocrine system diseases, eye diseases, female urogenital diseases and pregnancy complications, gastrointestinal disorders, hemic and lymphatic diseases, immune system diseases, male urogenital diseases, microbial diseases, musculoskeletal diseases, neoplasms, nervous system diseases, nutritional and metabolic diseases and disorders, occupational diseases, otorhinolaryngologic diseases, parasitic diseases, pathological conditions, psychiatric disorders, renal diseases, respiratory tract diseases, reproductive system diseases, skin and connective tissue diseases, stomatognathic diseases, urologic diseases, virus diseases, or wounds and injuries. [00139] In another embodiment, the authenticated pharmaceutical product comprises an active pharmaceutical ingredient which has not yet been approved for use by a regulatory agency. As new pharmaceuticals are discovered, it will become apparent to the skilled artisan to utilize the present invention to authenticate such new pharmaceutical products.

[00140] In certain embodiments, the authenticated pharmaceutical product is in a dosage form suitable for oral, parenteral, mucosal, topical/dermal, or inhalation route of administration. In some embodiments, the dosage form is a powder, liquid (e.g., syrup, solution), tablet, capsule, injection, cream, gel, lotion, film tab, spray, aerosol, suppository, or an ophthalmic preparation.

5.4.1. AUTHENTICATED TABLETS

[00141] Provided herein are authenticated pharmaceutical tablets comprising active

pharmaceutical ingredient(s), diamond nanoparticles, and one or more pharmaceutically acceptable excipients or carriers. In one embodiment, the pharmaceutically acceptable excipient(s) and carrier(s) is a filler (or a binder), a glidant, a disintegrant, a diluent, a lubricant, a dye (coloring agent), a flavoring agent, or any combination thereof.

[00142] Examples of fillers or binders include, but are not limited to, ammonium alginate, calcium carbonate, calcium phosphate, calcium sulfate, cellulose, cellulose acetate, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, erythritol, ethylcellulose, fructose, glyceryl palmitostearate, hydrogenated vegetable oil type I, isomalt, kaolin, lactitol, lactose, mannitol, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, medium chain triglycerides, microcrystalline cellulose, polydextrose, polymethacrylates, simethicone, sodium alginate, sodium chloride, sorbitol, starch (such as pregelatinized starch, STARCH 1500®) , sucrose, sugar spheres, sulfobutylether beta-cyclodextrin, talc, tragacanth, trehalsoe, polysorbate 80, and xylitol. In one embodiment, the filler/binder is microcrystalline cellulose. The

microcrystalline cellulose can be, for example, PROSOL V SMCC® 50, PROSOL V SMCC® 90, PROSOL V SMCC® HD90, PROSOL V SMCC® 90 LM, AVICEL PH 101, AVICEL PH 102, and any combination thereof.

[00143] Examples of glidants include, but are not limited to, calcium phosphate, calcium silicate, powdered cellulose, magnesium silicate, magnesium trisilicate, silicon dioxide, talcum and colloidal silica, and colloidal silica anhydrous. In one embodiment, the glidant is colloidal silica anhydrous, talc, or a combination thereof. [00144] Examples of disintegrants include, but are not limited to, hydroxypropyl starch, alginic acid, calcium alginate, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, powdered cellulose, chitosan, colloidal silicon dioxide, croscarmellose sodium, crospovidone, docusate sodium, guar gum, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, polacrilin potassium, povidone, sodium alginate, sodium starch glycolate, starch, and pregelatinized starch.

[00145] Examples of diluents include, but are not limited to, lactose (e.g., lactose monohydrate (FAST FLO® 316) and lactose anhydrous), cellulose (e.g., microcrystalline cellulose, such as AVICEL® PH 101 and AVICEL® PH 102).

[00146] Examples of lubricants include but are not limited to canola oil, hydroxy ethyl cellulose, lauric acid, leucine, mineral oil, poloxamers, polyvinyl alcohol, talc, oxtyldodecanol, sodium hyaluronate, sterilizable maize starch, triethanolamine, calcium stearate, magnesium stearate, glycerin monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil type I, light mineral oil, magnesium lauryl sulfate, medium-chain triglycerides, mineral oil, myristic acid, palmitic acid, poloxamer, polyethylene glycol, potassium benzoate, sodium benzoate, sodium chloride, sodium lauryl sulfate, stearic acid, talc, and zinc stearate.

[00147] In certain embodiments, provided herein are methods for the preparation of the authenticated pharmaceutical tablet. In one embodiment, diamond nanoparticles are combined with the active pharmaceutical ingredient(s) and the excipients that comprise the core of the tablet. The resulting mixture is then compressed into tablets by methods known in the art, such as wet granulation (e.g., mixing the powders with a liquid to form a moist granular mass, drying and sizing the agglomerates), dry granulation (e.g. passing the powder between rollers at high pressure followed by sizing the agglomerates) or direct compression (simple mixing of the powder ingredients). The tablets tagged with diamond particles are optionally film coated. A film coating is created by combining film components and colorants, and dissolving them in a suitable solvent. The coating is sprayed onto the tablet core by commonly known methods to form the final coated tablet.

[00148] In one embodiment, the method for preparing the tablet comprises: (i) weighing out the desired amount of active pharmaceutical ingredient(s), the desired amount of diamond

nanoparticles, and the desired amount of excipients; (ii) mixing or blending the diamond nanoparticles and the excipients, and combining the resulting mixture with the active pharmaceutical ingredient(s); (iii) mixing or blending the mixture of the active pharmaceutical ingredient(s), the diamond nanoparticles, and the excipients; (iv) passing the mixture of the active pharmaceutical ingredient, the diamond nanoparticles, and the excipients through a screen, and then remixing or reblending the resulting mixture; (v) compressing the mixture of the active

pharmaceutical ingredient, the diamond nanoparticles, and the excipients into a tablet form; and (vii) coating the compressed mixture of the active pharmaceutical ingredient, the diamond nanoparticles, and the excipients (i.e., the tagged tablet) with a coating agent to furnish the finished tagged-tablet.

[00149] In another embodiment, the authenticated pharmaceutical tablet is prepared by having the diamond nanoparticles combined with the components used in the coating of the tablet. A general method for preparing such a tablet comprises: (i) weighing out the desired amount of active pharmaceutical ingredient(s) and the desired amount of excipients; (ii) mixing or blending the active pharmaceutical ingredient(s) and the excipients; (iii) passing the mixture of the active pharmaceutical ingredient and the excipients through a screen, and then remixing or reblending the resulting mixture; (iv) compressing the mixture of the active pharmaceutical ingredient and the excipients into a tablet form; (v) weighing out the desired amount of diamond nanoparticles and coating agent(s); (vi) mixing or blending the diamond nanoparticles and the coating agent(s); and (vii) coating the compressed mixture of the active pharmaceutical ingredient and the excipients (i.e., the un-tagged tablet) with the mixture of the coating agent and the diamond nanoparticles (i.e., the diamond-tagged film coating) to furnish the finished tagged-tablet.

[00150] In certain embodiments, the tagged-tablet is contained in a packaging (e.g., blister pack, bottle, etc.), wherein the packaging is tagged with diamond nanoparticles from the same lot as that used to tag the tablet. The places on the packaging where the tagging is performed include, but are not limited to, product label, bar code, trade name, trade graphic, lot number, expiration date, and drug strength.

[00151] In one embodiment, the method for tagging the packaging comprises: (i) adding the diamond nanoparticles to the ink to be used to print the name of the active pharmaceutical ingredient on the packaging label; (ii) creating a suspension of the diamond nanoparticles in the ink using a suitable method known in the art (such as sonication, vigorous shaking, etc.); (iii) using the ink containing the diamond signature to print a label containing the name of the active

pharmaceutical ingredient; (iv) applying the tagged label to the packaging containing the tablet. [00152] In certain embodiments, provided herein are methods for verification of the active pharmaceutical ingredient in the tagged tablet. In one embodiment, the method for verifying the active pharmaceutical ingredient in the tagged-tablet comprises: (i) determining a spectral signature of the lot of diamond nanoparticles used in the tablet, before mixing the diamond particles with any other substance, or alternatively, determining the spectral signature in the final tagged tablet; (ii) remotely coding the spectral signature into handheld detectors; and (iii) using the detector to verify that the finished tagged-tablets contain the anticipated spectral signature. In one embodiment, the verification is done at the tablet manufacturing site.

[00153] In certain embodiments, provided herein are methods for verification of the tagged- packaging containing the tagged-tablets. In one embodiment, the method for verifying the tagged- packaging comprises: (i) determining a spectral signature of the lot of diamond nanoparticles used in the ink to print the label, before mixing the diamond particles with any other substance; (ii) remotely coding the spectral signature into handheld detectors; and (iii) using the detector to verify that the name of the active pharmaceutical ingredient on the packaging label contains the anticipated spectral signature. In one embodiment, the verification is done at the packaging line.

[00154] In an authenticated pharmaceutical tablet, the spectral signature of the tablet and the packaging are identical since the same lot of diamond material was used to tag the tablets and the packaging. A single, preprogrammed detector is used at any stage in the supply chain, e.g.

manufacturer's shipping department, wholesale warehouse or retail pharmacy, for field verification. Positive matches are obtained when scanning the name of the active pharmaceutical ingredient on the packaging and when scanning the tablets housed in the packaging.

5.4.2. AUTHENTICATED SYRUPS

[00155] Syrups are viscous aqueous solutions containing sugar or a sugar substitute. The concentration of sugar or sugar substitute in a syrup is close to the saturation point of the syrup. A syrup can be prepared by using heat, agitation, percolation or addition of a sugar or sugar substitute to a liquid medication. In a typical procedure, a sugar or sugar substitute and optionally other formulation excipients are added to water, and dissolved using heat, agitation or chemical means. The active pharmaceutical ingredient can be added prior to, in conjunction with, or after the addition of the other ingredients. The diamond nanoparticles can be dispersed in a separate container of syrup and added to the active pharmaceutical ingredient solution, or the diamond nanoparticles can be directly added to the active pharmaceutical ingredient solution, and mixed thoroughly to furnish the tagged syrup.

[00156] Tagging of the package containing the syrup, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.3. AUTHENTICATED CAPSULES

[00157] In certain embodiments, provided herein are authenticated pharmaceutical capsules. In one embodiment, the capsule is filled with a solid formulation (e.g., powder, granules) comprising the active pharmaceutical ingredient(s), diamond particles, and excipients. In another embodiment, the capsule is filled with a liquid formulation comprising the active pharmaceutical ingredient(s), diamond particles, and excipients. In another embodiment, the diamond particles are added to the components used in the making of the capsule, which is then filled with the formulation comprising the active pharmaceutical ingredient(s) and excipients.

[00158] Tagging of the package containing the capsules, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.4. AUTHENTICATED CREAMS

[00159] Creams are a type of emulsion. An emulsion is a dispersed colloidal system consisting of two immiscible liquid phases generally stabilized with one or more suitable agents. Creams are formulated from excipients that include oils (e.g. mineral oil, cotton seed oil, tea tree oil), fatty alcohols, fatty acids (e.g. stearic acid), and fatty esters. Emulsifying agents include nonionic surfactants (e.g. polysorbate 80), detergents (e.g. sodium laurel sulfate), and soaps. Preparation usually involves separating the formula components into two portions: lipid and aqueous. The lipid portion contains all water-insoluble components and the aqueous portion contains the water-soluble components. Both phases are heated to a temperature above the melting point of the highest melting component. The phases are then mixed and the mixture is stirred until reaching ambient temperature or until the mixture has congealed. Mixing is generally continued during the cooling process to promote uniformity. High-shear mixing, by homogenization or other means, is usually employed to reduce particle or droplet size and to improve the physical stability of the cream. The drug substance can be added to the phase in which it is soluble at the beginning of the

manufacturing process, or it can be added after the cream is prepared by a suitable dispersion process such milling with a roller mill. [00160] Diamond particles are readily suspended in aqueous liquids. The diamond nanoparticles or microparticles can be suspended separately in water and added to the aqueous portion of the emulsion before it is mixed with the lipid portion.

[00161] Tagging of the package containing the cream, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.5. AUTHENTICATED INJECTABLE DRUGS Liquid Formulation

[00162] The composition of an injectable drug that can be tagged in accordance with the invention includes the active agent (small molecule or biologic drug substance) dissolved in a suitable liquid that is usually buffered. The liquid is most often aqueous and contains a buffering agent to keep the pH in a suitable range (e.g. pH 4 - 8). Examples of buffers include citrate, histidine and phosphate. Other excipients, such as sodium chloride, may be included to maintain isotonic conditions. Injections must be free of pyrogens and must be sterile. These drug products must also meet limits on particulate matter (number of particles above 10 μπι and 25 μπι) per USP <1> or comparable compendial requirements. It is common to make the liquid buffer first and filter it to remove contaminants. The drug substance is then dissolved in the filtered buffer. Sterilization of the resulting drug solution is accomplished using methods known in the art.

[00163] Diamond particles, or a suspension of diamond particles, previously sterilized by methods known in the art are then aseptically added to the sterilized drug solution. The size of the diamond particles used to tag the drug solution must be larger than the pore size (generally, 0.2 μπι to 5 μπι) of the filter that will ultimately be used in the intravenous line for administering the infusion solution to a patient. In one embodiment, substantially all of the diamond particles used to tag the drug solution should be larger than the pore size of the intravenous filter that will be used for infusion so that substantially all diamond particles will be prevented from entering the patient's vein. In a preferred embodiment, all of the diamond particles should be of a size that is excluded by the intravenous in line filter to be used to infuse the patient.

[00164] Furthermore, since only a low concentration of diamond particles is required for authentication (e.g., see Figures 4 and 5, and Examples 3 and 4), only low concentrations (in the ppm or ppb range) of the diamond particles should be used to tag the drug solution. This provides the added advantage that the filter used in the intravenous line will not clog during administration of the drug to the patient. [00165] In this embodiment, diamond particles are present in the drug product for authentication during preparation, packaging, shipping, unpackaging, etc. However, the diamond particles are prevented from entering the patient's vein.

Lyophilized Powder (or cake)

[00166] The drug solution tagged with the diamond particles can be lyophilized using methods well known to those skilled in the art to form a powder or cake containing the drug and the diamond particles. Here, the authenticated drug for injection can be supplied (e.g., to a pharmacy) in the form of a lyophilized powder (or cake), which is reconstituted at an appropriate time and place (e.g., point of care, hospital, pharmacy, etc.). Here again, because the size of the diamond particles used to tag the drug solution is larger than the pore size (generally, 0.2 μιη to 5 μιη) of the filter used in the intravenous line for infusing a patient, the diamond particles will be prevented from entering the patient's vein.

[00167] Tagging of the package containing the injectable drug (whether a liquid injectable or a lyophilized preparation that is reconstituted at the point of care), and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

[00168] In an alternative embodiment, the diamonds are not removed. The composition of an injectable drug includes the active agent (drug substance) dissolved in a suitable liquid that is usually buffered. The liquid is most often aqueous and contains a buffering agent to keep the pH in a suitable range (e.g. pH 4 - 8). Examples of buffers include citrate, histidine and phosphate.

Other excipients, such as sodium chloride, may be included to maintain isotonic conditions.

Injections must be free of pyrogens and must be sterile. These drug products must also meet limits on particulate matter (number of particles above 10 μπι and 25 μπι) per USP <1> or comparable compendial requirements. It is common to make the liquid buffer first and filter it to remove contaminants. The drug substance is then dissolved in the filtered buffer. A suspension of diamond microparticles or nanoparticles is made in the same aqueous liquid used to dissolve the drug substance. The diamond solution is then added to, and mixed with, the already dissolved drug substance solution. Sterilization of the resulting drug solution is accomplished using methods known in the art. If sterilization is accomplished via filtration through filters with 0.2 μπι pore size, then the size of the diamond must be smaller than the pore size of the filter.

[00169] Tagging of the package containing the injectable drug, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154]. 5.4.6. AUTHENTICATED POWDERS

[00170] Powders are preparations consisting of solid, loose, dry particles of varying degrees of fineness. They contain one or more active pharmaceutical ingredients, with or without excipients and, if necessary, authorized coloring and flavoring agents. Powders tagged with diamond nanoparticles can be prepared by following the general procedure described in Section 5.4.1 prior to tablet formation (e.g., paragraph [00145]). The tagged powder formulation can be dosed in a packet, sachet, or vial.

[00171] Tagging of the package containing the powder, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.7. AUTHENTICATED SUPPOSITORIES

[00172] Suppositories are drug delivery systems containing one or more active pharmaceutical ingredients which are typically intended for application into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository). Suppositories are generally used for local action or systemic absorption of the active ingredient(s). They usually melt, soften, or dissolve at body temperature.

[00173] Suppositories are usually prepared from excipients or suppository bases such as cocoa butter, hard fat, glycerinated gelatin, hydrogenated vegetable oils and macrogols. They may also contain additives, such as adsorbents, surface-active agents, viscosity -influencing agents, antioxidants, antimicrobials, and authorized coloring agents. In a typical procedure, the active pharmaceutical ingredient(s) is combined with the suppository base(s), and the resulting formulation is processed into a suitable suppository by compression or molding techniques commonly used in the art. A tagged formulation for a suppository can be prepared by mixing diamond nanoparticles with the active pharmaceutical ingredient(s), followed by vigorous mixing with the base. Alternatively, the diamond particles are mixed with the base in a separate container, and the resulting mixture is combined with the active pharmaceutical ingredient(s). Suppositories can be prepared by molding or compressing a powdered tagged-formulation into a suitable shape, or by encapsulating a semi-solid tagged-formulation into soft gelatin. Molded suppositories can be obtained by pouring the tagged-formulation, sufficiently liquefied by heating, into suitable molds; the suppositories solidify on cooling. In certain cases, it is also possible to use the cold-molding compression procedure in a suitable press. [00174] Tagging of the package containing the powder, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.8. AUTHENTICATED AEROSOLS

[00175] Aerosols are dosage forms packaged under pressure that contain an active agent and a propellant that are released upon actuation of an appropriate valve system where the drug is released as a plume of fine particles or droplets. Typical components of aerosols are the

formulation containing one or more drug substance(s) and propellant, the container, the valve, and the actuator. Each component plays a role in determining various characteristics of the emitted plume, such as droplet or particle size distribution, uniformity of delivery of the therapeutic agent, delivery rate, and plume velocity and geometry. Aerosol preparations may consist of either a two- phase (gas and liquid) or a three-phase (gas, liquid, and solid or liquid) formulation. The two-phase formulation consists of drug substance(s) dissolved in liquefied propellant (e.g.

chlorodifluoromethane). Co-solvents such as alcohol (e.g., phenylethyl alcohol) may be added to enhance the solubility of the drug substance(s). Three-phase inhalation and nasal aerosol systems consist of suspended drug substance(s) in propellant(s), co-solvents (e.g. alcohols), and potentially other suitable excipients (e.g. carboxymethyl cellulose). The suspension or emulsion of the finely divided drug substance is typically dispersed in the liquid propellant with the aid of suitable biocompatible surfactants (e.g. polysorbate 80) or other excipients.

[00176] Diamond particles can be included during compounding by making a suspension of the diamond powder in the co-solvents (alcohols) or mixing the diamond particles with the other excipients before inclusion in the aerosol mixture.

[00177] Tagging of the package containing the aerosol, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.4.9. AUTHENTICATED OPHTHALMIC PREPARATIONS

[00178] Ophthalmic preparations are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside (intraocular) or adjacent (periocular) to the eye or used in conjunction with an ophthalmic device. Some of the commonly employed ophthalmic dosage forms include solutions, gel-forming solutions, suspensions, ointments, emulsions, gels, ocular inserts, and injections and implants for intraocular delivery. Tagged ophthalmic dosage forms are prepared by combining diamond nanoparticles with the active pharmaceutical ingredient(s) and the excipients, and processing the resulting tagged formulation into the desired dosage form by utilizing known methods. The process is carried out while satisfying the requirement for sterility as well as considerations for osmotic pressure (tonicity), preservation, tissue compatibility, the avoidance of pyrogens in intraocular dosage forms, particulate matter, and suitable packaging.

[00179] Tagging of the package containing the ophthalmic preparation, and the subsequent verification process can be conducted as described in paragraphs [00150] to [00154].

5.5. AUTHENTICATED GOODS

[00180] As described herein, the diamond particle based authentication system can be used in the authentication of various goods. In one embodiment, the authenticated goods are clothing, cosmetics, foods, consumer goods, mechanical parts, electronic parts, textiles, specialty paints, packaging or currency. In another embodiment, the clothing is designer clothing. In yet another embodiment, the foods are processed foods. In another embodiment, the authenticated goods are perfumes, wines or liquors.

5.5.1. AUTHENTICATED PERFUMES

[00181] Counterfeit fragrances are highly prevalent, and have been often found to contain chemicals that are health hazards. Authentication of fragrances by employing the invention method offers a solution to the problem.

[00182] In certain embodiments, provided herein are authenticated perfumes. In one

embodiment, the authenticated perfume comprises a perfume tagged with diamond particles wherein the perfume is selected from the group consisting of, but not limited to, Acqua di Parma, Agonist, Amouage, Annick Goutal, Atelier Cologne, Atelier Cologne, Baccarat, Bentley, Boadicea The Victorious, Bond No 9, Brunello di Montalcino, Byredo, Caron, Cartier, Chanel, Chantecaille, Cle de Peau Beaute, Clive Christian, CREED, Daum, Diana Vreeland, Dolce & Gabbana, Estee Lauder, EviDenS de Beaute, Ex Nihilo, Floris, Giorgio Armani, Givenchy, Guerlain, Hermes, Houbigant Paris, JAR, Jean Patou, Jo Malone London, Lalique, Loewe, Maison Francis Kurkdjian, Miller Harris, Molton Brown, Ormonde Jayne, Profumi del Forte, Ramon Monegal, Robert Piguet, Roja Parfums, Salvatore Ferragamo, Shalini, Sisley, Sisley-Paris, Thirdman, Tom Ford, Versace, Viktor & Rolf, Volnay, and Yves Saint Laurent. [00183] Labeling with diamond particles can be included in the perfume product (e.g., see Figures 4 and 5, and Examples 3 and 4) and/or on the packaging containing the perfume (e.g., as described in paragraphs [00150] and [00151]). A subsequent verification process can be conducted as described in paragraphs [00152] to [00154].

5.5.2. AUTHENTICATED WINES AND LIQUORS

[00184] Several scandals involving counterfeit wines and liquors have surfaced in recent times. Adulteration through dilution or by addition of cheaper products and harmful chemicals is common. Substitution of labels, with cheap poor quality products sold under the labels of more expensive wines and liquors is also highly prevalent. The present invention can be employed to authenticate wines and liquors, thereby addressing the highly prevalent issue of counterfeiting in such areas.

[00185] In certain embodiments, provided herein are authenticated wines. In one embodiment, the authenticated wine comprises a wine tagged with diamond particles, wherein the wine is selected from the group consisting of, but not limited to, Abreu Vineyard, Araujo, Bond Estates, Bryant Family, Colgin Cellars, Dalla Valle, Dana Estates, Diamond Creek, Futo, Ghost Horse, Grace Family Vineyards, Harlan Estate, Hundred Acre, Kapcsandy Family, Levy & McClellan, Lokoya, Marcassin Estate, Opus One, Paul Hobbs, Scarecrow, Schrader Cellars, Screaming Eagle, Sloan Proprietary Red, Verite, and ZD.

[00186] In another embodiment, the wine is selected from the group consisting of, but not limited to, Bruno Giacosa Barolo, Chateau Cheval Blanc, Chateau Lafite Rothschild, Chateau Lafleur, Chateau Latour, Chateau Latour a Pomerol, Chateau Le Pin, Chateau Mouton Rothschild, Chateau Petrus, Coche-Dury Les Perrieres, Chateau Rayas, Cheval Blanc, Domaine Armand Rousseau Pere et Fils Chambertin, Domaine Coche-Dury, Domaine de la Romanee-Conti, Domaine des Comtes, Domaine du Comte Liger-Belair, Domaine Dugat-Py, Domaine Dujac, Domaine Faiveley, Domaine Georges Roumier, Domaine Jean-Louis Chave, Domaine Leflaive Montrachet, Domaine Leroy, Domaine Leroy Clos de Vougeot, Domaine Leroy Corton-Renardes, Domaine Meo-Camuzet, Domaine Ramonet, Egon Miiller-Scharzhof, Emmanuel Rouget, Haut Brion, Henri Jayer, Jaboulet La Chapelle Hermitage, Joh. Jos. Priim, Krug Clos d'Ambonnay, Lafite, Lalou Bize- Leroy Domaine dAuvenay, Latour, Le Pin, Margaux, Mouton, Petrus, Ponsot, Quinta do Noval, Sassicaia, Schloss Reinhartshausen, Soldera Brunello di Montalcino, Sylvain Cathiard, and Vogue. [00187] In certain embodiments, provided herein are authenticated liquors. In one embodiment, the authenticated liquor is a whisk(e)y tagged with diamond particles, wherein the whisk(e)y is selected from the group consisting of, but not limited to, A.H. Hirsch, Angel's Envy, Ardbeg, Balvenie, Black Bowmore, Bulleit, Dalmore, Eagle Rare, Elijah Craig, George T. Stagg, Glen Grant, Glenfarclas, Glenfiddich, Glenglassaugh, Glenlivet, Glenmorangie, Glenmorangie Pride, Glenury Royal, Gordon & MacPhail Generations Glenlivet, Gordon & MacPhail Glen Grant, Hayman's Old Tom Gin, Highland Park, Jefferson's Bourbon, Jim Beam, Johnnie Walker,

Karuizawa, Lagavulin, Last Drop, Lost Prophet, Macallan, Michter's, Old Blowhard, Old Pulteney, Old Rip Van Winkle, Port Ellen, Pride Of Strathspey, Royal Salute, Talisker, William Larue Weller Kentucky, and Woodford Reserve.

[00188] Labeling with diamond particles can be included in the wine or liquor product (e.g., see Figures 4 and 5, and Examples 3 and 4) and/or on the packaging containing the product (e.g., as described in paragraphs [00150] and [00151]). A subsequent verification process can be conducted as described in paragraphs [00152] to [00154].

5.5.3. AUTHENTICATED ELECTRONIC PARTS

[00189] In certain embodiments, provided herein are authenticated electronic parts. In one embodiment, the authenticated electronic part comprises an electronic part tagged with diamond particles, wherein the electronic part is selected from the group consisting of, but not limited to, integrated circuits (ICs), microprocessors, memory ICs, programmable logic devices, transistors, capacitors, diodes, resistors, rectifiers, AC inverters, DC power supplies, transformers, resistors, relays, fuses, motor controllers, heaters, transmitters, compact discs, videotapes and DVDs, and computer software. In another embodiment, the electronic part includes any embedded software or firmware.

5.5.4. AUTHENTICATED MECHANICAL PARTS

[00190] In certain embodiments, provided herein are authenticated mechanical parts. In one embodiment, the authenticated mechanical part comprises a mechanical part tagged with diamond particles, wherein the mechanical part is utilized in the aerospace or defense industry. In another embodiment, the mechanical part is selected from the group consisting of, but not limited to, fasteners, connectors, bearings, studs, rings, shims, valves, springs, brackets, clamps, spacers, self- locking nuts, titanium aerospace parts, aluminum parts, assorted small parts, brake shoes, body armor, rotor retaining nuts, bolt hook point belts, and seatbelts.

5.5.5. AUTHENTICATED DESIGNER CLOTHING

[00191] In certain embodiments, provided herein are authenticated designer clothing. In one embodiment, the authenticated designer clothing comprises designer clothing tagged with diamond particles, wherein the clothing is selected from the designer group consisting of, but not limited to, Alexander Mcqueen, Armani, Balmain, Burberry, Calvin Klein, Chanel, Christian Louboutin, Dior, Dolce & Gabbana, Fendi, Gucci, Guess, Henry Aston Bespoke, Hermes International, Hugo Boss, John Varvatos, La Perla Lingerie, Lanvin, Louis Vuitton, Manolo Blahnik, Marc Jacobs, Missoni, Narciso Rodriguez, Prada, Ralph Lauren, Roland Mouret, Stella McCartney, Stuart Weitzman, Tom Ford, Tory Burch, Turnbull & Asser, Valentino, Versace.

5.5.6. AUTHENTICATED PROCESSED FOODS

[00192] In certain embodiments, provided herein are authenticated processed foods. In one embodiment, the authenticated processed foods comprise processed foods tagged with diamond particles, wherein the processed foods are made by an entity selected from the group consisting of, but not limited to, AdvancePierre, Agri-Mark, Agropur, American Crystal Sugar, American Foods Group, Anheuser-Busch InBev, Associated Milk Producers, Beam, Big Heart Pet Brands, Bimbo Bakeries, Borden Dairy, Boston Beer Co., Brown-Forman, California Dairies, Cal-Maine,

Campbell Soup, Canada Bread, Cargill, Chiquita, Chobani, Coca-Cola, Colgate-Palmolive, ConAgra, Constellation Brands, Cott, CROPP Cooperative, Dairy Farmers of America, Dannon, Darigold, Dean, Diamond, Dole, Dr. Pepper Snapple, E&J Gallo, Flowers, Foremost Farms, Foster Farms, General Mills, Gilster-Mary Lee, Glanbia, Golden State, Grassland Dairy, Great Lakes, H.J. Heinz, H.P. Hood, Hain Celestial, Hearthside, Hershey, Hillshire, Hilmar Cheese, Hormel, Hostess, J&J Snack Foods, J. R. Simplot, J.M. Smucker, JBS, Johnsonville, Kellogg, Keystone, Kraft, Lactalis, Lancaster Colony, Land O'Lakes, Leprino, Maple Leaf, Mars, McCain, McCormick, McKee, Michael, MillerCoors, Molson Coors, MOM Brands, Mondelez, Nestle, OSI Group, Parmalat, Pepsico, Perdue Farms, Pilgrim's Pride, Pinnacle, Post, Prairie Farms, Reser's, Rich Products, Sanderson Farms, Saputo, Sargento, Schreiber, Schwan Food, Seaboard, Seneca, Smithfield, Snyder's-Lance, TreeHouse, Tyson, Unilever, Wells, Weston, and WhiteWave.

[00193] Examples of processed foods include, but are not limited to: [00194] Baked goods and grains

Include, but are not limited to: White rice; Cornmeal; Polenta; Flour; White flour;

Bread; Rolls; Buns; Muffins; Bagels; Bread sticks; Pizza crust; Pita bread; Tortillas; Croutons; Flat bread; Crackers; Macaroni; Pasta; Couscous; Orzo; Cake; Cake mixes; Pie; Pie crust mixes; Cookies; Cookie dough; etc.

[00195] Salt and leavens

Include but are not limited to Salt; Baking powder; Baking soda; etc.

[00196] Processed fruits

Include but are not limited to Canned fruit; Frozen fruit; Fruit sauces; Jellies; Jams; Pie fillings; Fruit juice; etc.

[00197] Processed vegetables

Include but are not limited to Canned vegetables; Frozen vegetables; French fries;

Ketchup; Mustard; etc.

[00198] Convenience foods

Include but are not limited to Pizza; Precooked foods; Frozen dinners; Breakfast cereal; Granola; Energy bars; etc.

[00199] Processed meats

Include but are not limited to Canned meat; Cured meat; Ham; Lunch meat; Sausage; Bacon; Gelatins; Fresh meat with additives; etc.

[00200] Processed dairy foods

Include but are not limited to Cheese; Cheese food; Milk other than raw (homogenized, pasteurized, skim, low-fat, etc.); Yogurt; etc.

[00201] Processed fats and oils

Include but are not limited to Refined oils; Cooking spray; Margarine; Salad dressing; BBQ sauce; Mayonnaise; Peanut butter; etc.

[00202] Drinks

Include but are not limited to Soft drinks; Fruit drinks; Instant breakfast drinks; etc.

[00203] Confections

Include but are not limited to White sugar; Brown sugar; Corn syrup; Rice syrup; Honey (unless raw); Syrups; Candies; Soft candies; Pudding; Dessert mixes; Ice cream; Frozen desserts; Whipped cream; Chocolate; Marshmallows; Shredded coconut; Sugar substitutes; etc. 6. EXAMPLES

[00204] The following examples are offered to illustrate but not to limit the invention.

Example 1

Separation of Commercially Available Diamond Particles

[00205] Monocrystalline diamond particles were obtained from Sigma Aldrich. The product designation indicates the diameter of these particles to be in the micron range. The mixture was subjected to flow cytometry to obtain individual populations that are red, green or blue when exposed to UV light as follows:

[00206] One (1.0) gram of the monocrystalline synthetic diamond particles was pumped at a flow rate of 0.5 mL/min through a fluorescence spectrometer (LS-555, Perkin-Elmer, Co.) using a standard flow cell. The spectrum was measured at three different wavelengths corresponding to 410 nm (blue), 550 nm (green), and 675 nm (red) with a 10 nm bandwidth separation setting. The excitation slits were set to 5.0 nm and the emission slits were set to 10.0 nm. Material was continuously set to flow at a fixed rate.

[00207] After excitation from an Xe lamp through a single monochromator set to 363 nm and collimated, the light was passed through a polarizing filter then through the sample. Collection of each particle was performed mechanically after detection by a standard 950 PMT (Hamamatsu Co.) after separation by the emission monochromator. The desired population of red, green, and blue materials was collected by deflecting the particles out of the main stream by a piezo-electric device using a fluidic valve operating on one arm of a Y-shaped flow channel. The other channel collected the red material as well as any non-fluorescent materials. The final collection was 200 mg of blue, 350 mg of green and 450.0 mg of red material, representing 100% recovery.

[00208] The visible emissions of the separated red, green and blue particles when subjected to UV light are shown in Figure 1, slides 1-3. (Slides 4-6 are unseparated monocrystalline diamond from Sigma Aldrich, unseparated polycrystalline diamond from Sigma Aldrich and unseparated polycrystalline diamond from Mallinckrodt.) The loose bright material shown below the slides are particles of rare earth oxides YPV-F, from United Mineral Corporation, which is used a taggant, e.g., for currency or other documents, but is not used in pharmaceutical products. Example 2

Simple Labeling of Solid Dosage Forms

[00209] Using the separated particles prepared in Example 1, commercially available solid dosage forms were labeled with the individual populations by applying the separated particles with a Q-tip. Figure 2 shows a photograph of the results of this straightforward application of the diamond particles to the surface of a tablet when irradiated with UV light of 363 nm. Red, green and blue fluorescence is seen. When exposed only to visible light, no color was visualized.

[00210] The red and blue populations prepared in Example 1 were also used to label

commercially available tablets comprising similar fillers in a blister pack. As shown when exposed to UV light, red and blue populations are distinguishable through the blister. When exposed only to visible light, no color was visible.

Example 3

Visual Appearance in Suspension

[00211] As shown in Figure 4, the particles were resuspended in water in cuvettes. From left to right, these contain the green only, red only, red:green (approximately 1 :5), and red:green:blue (approximately 1 :4:2), all at 10 mg/ml. While the red and red:green (1 :5) material appear to be the same, their spectral signatures are easily distinguished as shown in Figure 6 (see Example 4).

Example 4

Emission Spectra of Components

[00212] Fifty (50.0) mg of separated red, green and blue particles were suspended in purified water and placed into 1.0 cm square quartz cuvettes. The cuvettes were placed into a Photon Counting Machine (PTI, Inc.). The measurements were taken using a double excitation and double emission monochromators and a 400 nm long pass filter on the emission monochromator. Both mono gratings were 600 lines/cm with a blaze angle of 1.0 micron. Detection was achieved using a 950p photomultiplier tube (Hamamatsu Co.). Excitation measurements were taken using an excitation algorithm and setting the emission monochromator to the maximum of each material and scanning the excitation from 300 nm to 450 nm, with results shown in Figure 5.

[00213] The excitation wavelength for material fluorescing at all three colors was similar. The blue emission maximum was about 445 nm, the other peaks were likely due to green and red contamination. The emission spectra for green and red fluorescing materials appeared not to be contaminated by material that fluoresced at other wavelengths. The red emission spectrum contained some characteristic fine detail at 575 nm and 590 nm.

[00214] Further measurements were taken in a similar manner using mixtures of the previously separated materials. It can be seen that each material that was mixed retains its unique spectrum in the visible range as shown by the emission spectrum in Figure 6.

[00215] These spectra were obtained by setting the excitation monochromator in the

spectrophotometer at 360 nm. An additional (fifth) spectrum arising from the red:green:blue fluorescing mixture, also shown in Figure 6, was obtained by exciting the material, instead, with light from a hand held LED source at 365 nm. This spectrum appeared more intense because the LED source, as opposed to light from the excitation monochromator, flooded the sample chamber. Mixtures of these materials, surprisingly, retained, in the visible range, the characteristic spectral signatures of each component of the mixture. Rather than a single broad emission spectrum, one can clearly distinguish separate red, green and blue emissions in the red:green:blue mixture and red and green emissions in the red:green mixture.

Example 5

Visibility in Dosage Forms

[00216] Figure 7 is a photograph, taken under UV light, of tablets comprised of calcium carbonate, hydroxypropyl cellulose and Avicel™ and approximately 1 mg/10,000 mg of red, green or blue material. This works out to about 0.1 mg or 100 micrograms of particles per tablet. As seen, these fluoresce in various colors; while under visible light these tablets appear identical. Tablets that do not contain taggant or contain taggant that does not appear to fluoresce in the visible range appear black. However, tablets that contain unseparated mixtures of diamond particles appear black but are easily detectable by infrared fluorescence in the range of 850-1,200 nm, enabling forensic or covert encryption.

[00217] Figure 8 shows both the emission and excitation spectra of a tablet which contains a mixture of synthetic diamond particles at 100 ppm. Due to the interference of fluorescence from the various types of particles (e.g., red, blue or green), the tablets appear black and a spectrum obtained by irradiation with UV light at 365 nm in the 400 nm-700 nm range is essentially null as shown in Figure 9. However, as shown in Figure 8, there are characteristic peaks in the range of 850-1, 120 nm in the infrared range which can be displayed when irradiated with light in the visible range, in particular in the range of 400-500 nm, 500-650 nm and 800 nm. A particularly strong peak at 880 nm is essentially an artifact of the spectrometer since the "emission" also includes reflected excitation light. The intensity of each peak in the IR range will depend on the excitation wavelength chosen and its intensity.

Example 6

Comparison of Variously Labeled Tablets

[00218] Tablets comprised of standard fillers were prepared containing 100 ppm of various separated diamond particles or, as a control, unseparated mixtures of fluorescent diamond particles. As described in Example 1, the diamond mixtures were obtained from Sigma Aldrich and separated into red, green and blue fluorescence using flow cytometry. Eight different test tablets were prepared in addition to a control tablet which contains 100 ppm of unseparated diamond. The tablets were glued with transparent glue to a slide that has been painted black for better viewing.

[00219] All of the tablets (except those labeled "speck" in Figure 10) were prepared as follows. For those labeled "speck," magnesium stearate was used instead of stearic acid.

Ingredient W, (%) SuppHer p onding

FIPMC (hydroxypropyl 69.9990 Dow Chemical 0.69999

methylcellulose)

Paracetamol 13.2000 BASF 0.132

Calcium Carbonate 5.0000 Dow Chemical 0.05

Ludipress^® 3.0000 BASF 0.03

Kollidon^® CL 3.0000 BASF 0.03

PEG 6k 5.0000 Hexion 0.05

Stearic Acid 0.8000 Sigma Aldrich 0.008

Diamond particles 0.0010 Persis Science, LLC 0.00001

Total : 100.0000 1.

All components were mixed in a speed-mixer, sieved through 325 mesh screen and pressed with low compression. Total weight per tablet 680 mg, 13 mm diameter, and diplanar in form.

[00220] Figure 10 shows the visible colors resulting from excitation at 365 nm. From left to right, the first tablet contains only red-fluorescing diamond particles, the second contains red- fluorescing particles with a trace of green and blue particles, the third contains an unseparated mixture of the original diamond particles before exposure to flow cytometry to separate colors, the fourth is a tablet tagged with only green-fluorescing particles, the fifth is a tablet tagged with only blue-fluorescing particles, the sixth is a tablet which contains equal amounts of red-, green- and blue-fluorescing particles and appears yellow, the seventh is a tablet that contains red-fluorescing particles with a trace of green and blue and also contains magnesium stearate as a component of the tablet itself, the eighth is a similar tablet containing magnesium stearate with an equal mixture of green- and blue-fluorescing particles and the ninth is a tablet also with an equal mixture of green- and blue-fluorescing particles but with stearic acid rather than magnesium stearate. The total level of diamond nanoparticles in all nine tablets is 100 ppm.

[00221] In all the following spectra, the y-axis measures the intensity in counts per second in the spectrophotometer.

[00222] The individual spectra of the red-labeled tablets, the green-labeled tablets and the blue- labeled tablets are shown superimposed on Figure 11. These spectra were obtained using a photomultiplier tube with 1,200 lines/cm and a 300 blaze angle. The emission was read at an angle of 44° from the excitation beam.

[00223] Figure 12 shows the spectrum obtained in the same way for the second tablet from the left which contains red with a trace of green and blue. This is expanded in the range of 400-550 nm in Figure 13 so that the contribution of the green and blue portions of the spectrum can be more accurately determined.

[00224] Figure 14 shows superimposed spectra in the 400-700 nm range for all of the nine tablets depicted in Figure 10. Of particular interest is the spectrum of the yellow tablets which shows distinct peaks in the red wavelength, the green wavelength and blue wavelength. The intensities of these are similar to those depicted in Figure 1 1, except that the intensity of the blue portion of the spectrum appears more widely distributed over the wavelength band.

[00225] The data shown in these figures is compiled in Figure 15 which integrates the number of photons over the entire spectrum (shown in blue) or over the relevant peaks (shown in red). In all cases, the red peak values will be smaller because they cover only the relevant range rather than the entire spectrum.

[00226] Reading from left to right in Figure 15, the control is integrated over the entire

400-700 nm regions and is very low. A comparison between the range (400-700 nm) integration with the peak pick integration shows the specificity of the emitted wavelength. Thus, for the pure red-labeled tablets shown in the fourth set of bars, the integration over the entire range shows that the red peak accounts for most of the total intensity and the integration over 400-570 nm which excludes the red peak is minimal. Similarly, the pure green and pure blue labeled tablets, shown in the succeeding fifth and sixth comparisons, shows that most of the integration over the entire range is due to the individual green or blue peak. Turning back to the second and third from left comparisons where a red labeled tablet has a trace of green and blue, the integration over the red peak again offers a substantial portion of the overall integrated count, and the trace blue and green component relatively little (400-570 nm).

[00227] With respect to the results for yellow labeled tablet, each of the red, blue and green peaks were summed to obtain the peak pick integration shown in red. The intensity over the entire range for the yellow labeled tablet is shown in blue and is not very different from the peak pick integration. With regard to the tablets that contain magnesium stearate which show a speckled appearance, it is clear that the overall spectrum is much less defined in terms of individual peaks by comparing the red and blue bars. The concentration of colors in the blue and green peaks is shown in the tenth set of bars and the same tablet but with the intensities divided by 10 is shown in the last set of bars. This shows that 10 ppm could readily be determined on the equipment employed. Clearly, the lower level of detection will depend on the design of the spectrophotometer and the settings used.

Example 7

Manufacture of a film coated tablet

Tagging the tablet

[00228] The diamond nanoparticles are combined with the inactive ingredients and the active agent that comprise the core of the tablet. The inactive ingredients (e.g., microcrystalline cellulose, lactose monohydrate, tribasic calcium phosphate, crospovidone, magnesium stearate) are combined in a suitable container and mixed as dry powders with a total weight of 1000 g. In a separate container, diamond nanoparticles (1 g - 10 g) are combined with a small amount of the inactive ingredient mixture (50% each by weight; i.e. 1 g diamond material + 1 g premixed inactive ingredients). The diamond mixture is then added to the original container with the inactive ingredients, and all the contents in the container are mixed thoroughly. A therapeutically effective amount of the active pharmaceutical ingredient is added to the inactive ingredient/diamond material, and mixed thoroughly. This final mixture is sieved and then compressed into tablets using methods well known in the art of tablet preparation. Alternatively, the final mixture can be wet granulated by utilizing methods well known in the art, and then dried to form agglomerates of a size that readily compress into tablets. The core tablet containing the active agent is now tagged with diamond nanoparticles. A film coating is created by combining film components (e.g., hypromellose, triacetin, titanium dioxide) and colorants (e.g., yellow ferric oxide, red ferric oxide), and dissolving in a suitable solvent (e.g., water). The coating is sprayed onto the tablet core, utilizing methods well known in the art, to form the final coated tablet.

[00229] In another method of preparing a tagged tablet, the diamond nanoparticles are combined with the components used in the film coating. To form the core, the inactive ingredients (e.g., microcrystalline cellulose, lactose monohydrate, tribasic calcium phosphate, crospovidone, magnesium stearate) are combined and mixed as dry powders with a total weight of 1000 g. A therapeutically effective amount of the active pharmaceutical ingredient is added to the inactive ingredients, and mixed thoroughly. This final mixture is sieved and then compressed into tablets using methods well known in the art of tablet preparation. Alternatively, the mixture can be wet granulated by utilizing methods well known in the art, and then dried to form agglomerates of a size that readily compress into tablets. A film coating is created by combining its components (e.g., hypromellose, triacetin, titanium dioxide) and colorants (e.g., yellow ferric oxide, red ferric oxide) and dissolving thoroughly in a suitable solvent (e.g., water). Diamond particle material (1 g - 10 g) is added to the film coating solution, and dispersed by sonication or other rapid dispersion method. The core tablet is then sprayed with the diamond-tagged film coating to produce the final drug product.

Tagging the packaging

[00230] The general method for tagging the packaging with diamond material is described in paragraphs [00150] and [00151]. Diamond nanoparticles from the same lot as that used to tag the tablet are added to the ink to be used to print the name of the active pharmaceutical ingredient on the bottle label. The diamond nanoparticle material is added to the ink at a desired amount. A suspension of the diamond particles in the ink is created by sonication or other rapid dispersion methods such as vigorous shaking. The label is printed using standard equipment and procedures where the ink containing the diamond signature is used only to print the words corresponding to the name of the active pharmaceutical ingredient. The label is applied to the bottle containing the tablets per standard automated processes.

Verification

[00231] Verification in the drug product tablet: The spectral signature of the lot of diamond nanoparticles used in the tablet and label is determined before mixing the diamond particles with any other substance. This spectra signature is then remotely coded into handheld detectors. After manufacture of the tablets, a detector is used to verify that the final tablets contain the anticipated spectral signature; this can be done at the tablet manufacturing site on the bulk tablets and/or at the packaging line when the tablets are placed in bottles.

[00232] Verification of the package : The spectra signature embedded in the name of the active pharmaceutical ingredient is read on the bottle label using a preprogrammed detector at the packaging line.

[00233] Verification of the 1:1 correspondence : The spectral signature of the tablet and the package are identical since the same lot of diamond material is being used to tag the tablets and the bottle label. A single, preprogrammed detector is used at any stage in the supply chain, e.g.

manufacturer's shipping department, wholesale warehouse or retail pharmacy, for field verification. Positive matches should be obtained when scanning the words corresponding to the name of the active pharmaceutical ingredient on the bottle label, and when scanning the tablets housed in the bottle.

[00234] The above described method for the manufacture of an authenticated tablet could be applied for the preparation of tablets whose active pharmaceutical ingredient is, without limitation, rosuvastatin, esomeprazole, aripiprazole, clopidogrel, duloxetine, escitalopram, amphetamine, armodafinil, modafinil, amlodipine, simvastatin, amoxicillin, sildenafil, flibanserin, or a

pharmaceutically acceptable salt, clathrate, solvate, tautomer, isotopologue, prodrug, stereoisomer, or combination of any of the foregoing.

Example 8

Liquid formulation for oral administration

Tagging the drug product

[00235] Methods of preparing a pharmaceutical liquid formulation for oral administration are well known in the art. A diamond tagged liquid formulation suitable for oral administration is prepared by adding diamond particle suspension to a solution of the active pharmaceutical ingredient. A volume of 1000 mL of a syrup is prepared by adding to a container disodium edetate, fructose (200 mg/mL), dl-lactic acid, methyl paraben, propylene glycol, propyl paraben, sucrose (400 mg/mL), and suitable flavoring agent(s). All the ingredients are stirred well, and NaOH is added as needed to dissolve all excipients. The active pharmaceutical ingredient is added at a therapeutically active concentration, and dissolved in 900 mL of the syrup. In a separate container, 1 mg diamond nanoparticles is dispersed in 100 mL syrup. The active pharmaceutical ingredient solution and the diamond solution are combined, and mixed thoroughly to furnish the tagged syrup.

[00236] Tagging of the package containing the liquid formulation, and the subsequent verification process are conducted as described in paragraphs [00150] to [00154].

[00237] The above described method for the preparation of an authenticated liquid formulation could be applied for the preparation of liquid formulations whose active pharmaceutical ingredient is, without limitation, aripiprazole, amoxicillin, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, isotopologue, prodrug, stereoisomer, or combination of any of the foregoing.

Example 9

Film tab for mucosal administration

Tagging the drug product

[00238] Methods of preparing film tabs for mucosal administration are well known in the art. A diamond tagged film tab for mucosal administration is prepared by adding diamond particles (concentration range of 0.001% to 0.01%) to the polymer mix that makes up the tab before the tab is made, thereby ensuring that the diamond particles are equally dispersed in the film. Components of the film, including active pharmaceutical ingredient, polyethylene oxide, hydroxypropyl methylcellulose, maltitol, acesulfame potassium, lime flavor, citric acid, sodium citrate, and FD&C yellow #6, are mixed thoroughly. To this mixture is added the diamond material, and the resulting mixture is processed to make the film by utilizing methods well known in the art.

Tagging the package

[00239] The films prepared above are placed in suitable packaging, which is tagged with diamond material as described in paragraphs [00150] and [00151].

[00240] The verification process is conducted as described in paragraphs [00152] to [00154].

[00241] The above described method for the preparation of an authenticated film tab could be applied for the preparation of film tabs whose active pharmaceutical ingredient is, without limitation, buprenorphine, naloxone, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, isotopologue, prodrug, stereoisomer, or combination of any of the foregoing. Example 10

Nasal spray for mucosal delivery

Tagging the drug product

[00242] Methods of preparing a nasal spray for mucosal delivery are well known in the art. A diamond tagged nasal spray for mucosal delivery is prepared by combining diamond particles (concentration range of 0.001% to 0.01%>) with an aqueous suspension of the active pharmaceutical ingredient and excipients comprising the formulation. The active pharmaceutical ingredient and inert ingredients - microcrystalline cellulose, carboxymethyl cellulose sodium, 0.02% w/w benzalkonium chloride, polysorbate 80, 0.25% w/w phenul ethyl alcohol - are mixed thoroughly to create an aqueous suspension (pH 5 - 7). In a separate container is prepared a suspension of diamond particles in a small amount of the same inert ingredient mixture. The suspension containing the diamond mixture is added to the suspension containing the active pharmaceutical ingredient, and the resulting suspension is mixed thoroughly. The tagged formulation is processed into a nasal spray by utilizing methods well known in the art.

[00243] Tagging of the package containing the formulation prepared above, and the subsequent verification process are conducted as described in paragraphs [00150] to [00154].

[00244] The above described method for the preparation of an authenticated nasal spray could be applied for the preparation of nasal sprays whose active pharmaceutical ingredient is, without limitation, fluticasone propionate.

Example 11

Lotion for topical administration

Tagging the lotion

[00245] Methods of preparing a lotion for topical administration are well known in the art. A diamond tagged lotion for topical administration is prepared by adding diamond particles

(concentration range of 0.001%> to 0.01%>) to the lotion base containing the active pharmaceutical ingredient and excipients. The inactive ingredients - hydroxypropyl cellulose, isopropyl alcohol (30%)), propylene glycol, purified water, and sodium phosphate monobasic, monohydrate are combined in a vessel. To this mixture are added diamond particles at a concentration of 0.01%>, and the active pharmaceutical ingredient at a therapeutically effective concentration. The contents are mixed using high shear to emulsify, while adding phosphoric acid as needed until pH is

approximately 7. Tagging the packaging

[00246] The lotion is packaged in plastic bottles with a label on the bottle. As described in paragraphs [00150] and [00151], diamond nanoparticles can be included in the ink used to print batch-specific information on the label (i.e., bar code, unique ID number, lot number or expiration date).

[00247] The verification process is conducted as described in paragraphs [00152] to [00154].

[00248] The above described method for the preparation of an authenticated lotion could be applied for the preparation of lotions whose active pharmaceutical ingredient is, without limitation, betamethasone dipropionate.

Example 12

Liquid formulation (biologic) for intravenous administration Tagging the drug product

[00249] Methods of preparing a biologic liquid formulation for intravenous administration are well known in the art. A diamond tagged biologic liquid formulation for intravenous

administration is prepared by adding diamond nanoparticles (concentration range of 0.001% to 0.01%)) to a solution of the pharmaceutically active biologic just before sterile filtration. A buffer solution (pH 6.5) is prepared by combining polysorbate 80 (0.7 mg/mL), sodium chloride ( 9mg/mL), sodium citrate dehydrate (7.35 mg/mL), and WFI (water for injection). The buffer solution is then filtered. The pharmaceutically active biologic is added at a therapeutically effective amount. The pharmaceutically active biologic is then buffer exchanged while keeping the concentration at about 10%> higher than the target concentration. Separately, a diamond suspension is prepared by using a batch of diamonds with a particle size distribution where D50 is

approximately lOOnm and D90 < 200nm. The diamond nanoparticles are suspended in the same buffer as the biologic active ingredient at lOx concentration (0.1%> - 0.01%>), and the resulting suspension is filtered. The resulting diamond filtrate is then added to the biologic active ingredient solution (1 :9 v/v), and thoroughly mixed. The tagged formulation is sterilized by an acceptable means known in the art, which is followed by aseptic fill and finish procedures known in the art. The diamond spectral signature can be read through the clear glass vial.

[00250] Liquid drugs for injection that contain small molecules, nucleotides, antibody drug conjugates and other non-biologic active agents, without limitation, can be prepared and tagged with diamond particles in a manner similar to that described for biologies. [00251] Tagging of the package containing the formulation prepared above, and subsequent verification process are conducted as described in paragraphs [00150] to [00154].

[00252] The above described method for the preparation of an authenticated injectable could be applied for the preparation of injectables whose active pharmaceutical ingredient is, without limitation, rituximab.

[00253] As illustrated above, the invention provides the following embodiments: (In all cases below "product" also includes packaging and intermediates.)

[00254] The invention provides a method for providing authentication to a product which method comprises combining said product with a prescribed form of an authentication system which comprises at least one population of diamond particles wherein said particles exhibit fluorescence, and wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy; in some embodiments the population is homogeneous.

[00255] The method also includes an embodiment wherein said combining is with at least two homogeneous populations of said particles, wherein the fluorescence wavelength, intensity, duration or any combination is unique to each said different population.

[00256] In addition the method includes an embodiment wherein, in addition to at least one homogeneous population(s), the product is combined with a heterogeneous population of diamond particles, or the product may be combined only with a heterogeneous population.

[00257] In all of these cases, the populations are optionally distributed within the product, or the product may be a solid having a surface and the populations are disposed on the surface of the solid. If the latter, the populations may be disposed in a predetermined pattern on said surface.

[00258] The invention further includes a product prepared by any of the above methods. The product may be a pharmaceutical product, and may be in solid oral dosage form.

[00259] The above product may optionally be associated with a code designating the excitation wavelength(s) and/or duration(s) and/or intensity(ies) that cause said population(s) to fluoresce and/or identifies the emission wavelength(s) and/or duration(s) and/or intensity(ies), which code may be secret.

[00260] The invention also includes a method to authenticate a product to be tested which method comprises irradiating the product with excitation wavelength(s), duration(s) and intensity(ies) that generate(s) fluorescence from said population(s) of diamond particles and observing said fluorescence. In one typical embodiment a spectrum comprising both wavelength and intensity from each population may be observed.

[00261] In the above authentication methods, said test product spectrum may be evaluated visually or by use of a spectrophotometer or by use of a detector programmed to consider only predetermined spectral parameters including a detector comprising an interrogation device either on site or spectral data may be transmitted to a data center providing an interrogation device.

[00262] The invention thus includes a product which comprises a prescribed form of the described above authentication system wherein said authentication system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy.

[00263] In one embodiment, the diamond population in the prescribed form of authentication system used in the product is homogeneous; in another embodiment, the prescribed form comprises at least two different homogeneous populations of fluorescent diamond particles; wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof. The product may include in the authentication system heterogeneous population of diamond particles, or may contain only said heterogeneous population. The product may have the populations of particles distributed throughout the composition, or if the composition is a solid, and the solid has a surface, the particles may be, but need not be, at the surface of the product.

[00264] In the latter case, the authentication system may optionally be distributed in a preset pattern, such as a number or letter. For products that are solids, the product may comprise a hydrophilic base in combination with a hydrophobic hygroscopic component, that optionally has been subjected to pressure to expel water from the hydroscopic component. Any of these products may be a pharmaceutical product. Any of these products may have associated therewith a code designating excitation wavelength(s), and/or duration(s) and/or intensity(ies) to be employed in authenticating the product, and the code for the excitation wavelength(s) and/or duration(s) and/or intensity(ies) may optionally be secret.

[00265] The invention also includes a method to authenticate a product which method comprises irradiating said product with excitation wavelength(s), duration(s) and intensity(ies) that generate(s) fluorescence from said population(s) of diamond particles and determining any fluorescence. In some instances, a spectrum comprising both wavelength and intensity and optionally duration of emissions from each population is determined. [00266] The spectrum may also be transmitted to a data center or a detector programmed to recognize authentic spectra, which detector may be remote from the end user.

[00267] The invention is also directed to certain authentication systems comprising particulate diamond populations per se.

[00268] The invention includes:

1. A prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy,

wherein said prescribed form comprises at least two different homogeneous populations of fluorescent diamond particles; and

wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof, or

wherein said prescribed form comprises at least one population that is homogeneous and at least one population that is heterogeneous.

2. A product which comprises the prescribed form of paragraph 1.

3. A product which comprises a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the

wavelength, duration and intensity of the excitation energy,

wherein said prescribed form consists of one homogeneous population of diamond particles or consists of a heterogeneous population of said particles.

4. The product of paragraph 2 or 3 which is associated with a code designating the excitation wavelength(s) and/or duration(s) and/or intensity(ies) that cause said population(s) to fluoresce, and/or designates the wavelength(s) and/or duration(s) and/or intensity(ies) of the fluorescent emission of the prescribed form.

5. The product of paragraph 4 wherein said code is secret and disclosed only to designated recipient(s). 6. The product of paragraph 2 or 3 wherein the prescribed form of authentication system is distributed throughout the product.

7. The product of paragraph 2 or 3 which is a powder, semisolid, emulsion or liquid.

8. The product of paragraph 2 or 3 which is a solid.

9. The product of paragraph 8 wherein the solid has a surface and the prescribed form of the authentication system is at the surface of the composition.

10. The product of paragraph 9 wherein the authentication system is distributed in a preset pattern.

11. The product of paragraph 8 which comprises a hydrophilic base in combination with a hydrophobic hygroscopic component.

12. The product of paragraph 11 which has been subjected to pressure to expel water from the hydroscopic component.

13. The product of paragraph 2 or 3 which is a pharmaceutical composition.

14. The product of paragraph 13 wherein the composition is a topical, an oral composition or a parenteral composition.

15. The product of paragraph 13 which is a solid oral dosage form.

16. The product of paragraph 2 or 3 which is a cosmetic, fragrance, ink, luxury item, food, textile, mechanical part, paint or a document of value.

17. A method to evaluate a test product for authenticity, which method comprises irradiating said product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product described in paragraph 2 or 3 and determining any fluorescence emitted; and comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product.

18. The method of paragraph 17 wherein said determining and comparing is by eye.

19. The method of paragraph 17 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

20. The method of paragraph 19 wherein said spectral data are transmitted to an interrogation device for said comparing or spectral data determination and interrogation are included in the same apparatus.

21. The method of paragraph 20 wherein the interrogation device is programmed to compare spectral data of the test product to spectral data characteristic of the prescribed form of authentication system in the authentic product; wherein said comparing determines the product as authentic if the spectral data match and counterfeit if the spectral data do not match.

22. The method of paragraph 20 or 21 wherein said interrogation device is remote from the detector determining the spectral data.

23. The method of paragraph 20 or 21 wherein the interrogation and spectral data determination are included in the same apparatus.

24. A method for providing authentication to a product which method comprises combining said product with a prescribed form of the authentication system of paragraph 1, or with one homogeneous population of diamond particles or a heterogeneous population of diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy.

The invention is not to be limited in scope by the embodiments disclosed in the examples which are intended as single illustrations of individual aspects of the invention, and any methods which are functionally equivalent are within the scope of the invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims.

Claims

What is claimed is:

1. A product which comprises an active pharmaceutical ingredient and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of an excitation energy, wherein:

(a) the active pharmaceutical ingredient is listed in Table 2, and

(b) said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

2. The product of claim 1 in which the prescribed form of the authentication system is also incorporated into a label, barcode, or both, affixed to the product packaging.

3. A method to evaluate a pharmaceutical product for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 1 or 2.

4. The method of claim 3 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

5. A product which comprises a wine or liquor and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy, wherein:

(a) the wine or liquor is listed in Section 5.5.2, and

(b) said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

6. The product of claim 5 in which the prescribed form of the authentication system is also incorporated into a label, barcode or both affixed to the product packaging.

7. A method to evaluate a wine or liquor listed in Section 5.5.2 for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 5 or 6.

8. The method of claim 7 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

9. A product which comprises a cosmetic or fragrance and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of the excitation energy, wherein:

(a) the cosmetic or fragrance is a perfume listed in Section 5.5.1, and

(b) said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

10. The product of claim 9 in which the prescribed form of the authentication system is also incorporated into a label, barcode or both affixed to the product packaging.

11. A method to evaluate a cosmetic or fragrance listed in Section 5.5.1 for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 9 or 10.

12. The method of claim 11 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

13. A product which comprises clothing and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of an excitation energy, wherein:

said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

14. The product of claim 13 in which the prescribed form of the authentication system is also incorporated into a label, barcode, or both, affixed to the product packaging.

15. A method to evaluate clothing for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 13 or 14.

16. The method of claim 15 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

17. A product which comprises a processed food and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of an excitation energy, wherein:

said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

18. The product of claim 17 in which the prescribed form of the authentication system is also incorporated into a label, barcode, or both, affixed to the product packaging.

19. A method to evaluate a processed food for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 17 or 18.

20. The method of claim 19 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

21. A product which comprises a mechanical or electronic part and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of an excitation energy, wherein: said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

22. The product of claim 21 in which the prescribed form of the authentication system is also incorporated into a label, barcode, or both, affixed to the product packaging.

23. A method to evaluate a mechanical or electronic part for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 21 or 22.

24. The method of claim 23 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.

25. A product which comprises a consumer good and a prescribed form of an authentication system which system comprises at least one population of fluorescent diamond particles wherein the wavelength, duration and intensity of the fluorescence emission of said particles is dependent on the wavelength, duration and intensity of an excitation energy, wherein: said prescribed form of the authentication system comprises one or more homogeneous populations of diamond particles, one or more heterogeneous populations of diamond particles, or a mixture of one or more homogeneous and one or more heterogeneous populations of diamond particles, wherein each different population has a unique fluorescence wavelength or intensity or duration or combination thereof that generates a signature signal.

26. The product of claim 25 in which the prescribed form of the authentication system is also incorporated into a label, barcode, or both, affixed to the product packaging.

27. A method to evaluate a consumer good for authenticity, comprising irradiating a test product with (an) excitation wavelength(s), of certain duration(s) and intensity(ies) that generate(s) fluorescence from the population or populations of diamond particles in the prescribed form of the authentication system contained in the authentic product and determining any fluorescence emitted; and

comparing said fluorescence of the test product with that characteristic of the prescribed form of authentication system that is contained in the authentic product of claim 25 or 26.

28. The method of claim 27 wherein a spectrum comprising wavelength and intensity and optionally duration of the fluorescent emission of said test product is determined using a spectrophotometer or spectral data are determined with a detector.