WO2014117236A1

WO2014117236A1 - Oil-in-water nanoemulsion and process for producing same

Info

Publication number: WO2014117236A1
Application number: PCT/BR2014/000023
Authority: WO
Inventors: Claudia Regina ELIAS MANSUR; Eduardo RICCI JÚNIOR; Vânia Emerich BUCCO DE CAMPOS; Juliana PERDIZ SENNA
Original assignee: Universidade Federal Do Rio De Janeiro - Ufrj
Priority date: 2013-01-30
Filing date: 2014-01-30
Publication date: 2014-08-07
Also published as: BR102013002259A2

Abstract

The present invention describes an oil-in-water nanoemulsion consisting of 5-40% m/m (mass/mass percent) of at least one surfactant, 1-50% m/m of at least one oil; and optionally approximately 30% of one or more solvents; the invention also describes the production process and the use as carrier of hydrophobic compounds, which can be pharmaceuticals, cosmetics, vitamins or nutritional compounds.

Description

NANOEMULSION OIL IN WATER AND ITS PRODUCTION PROCESS FIELD OF THE INVENTION

The present invention belongs to the field of nanotechnology, specifically to the field of manufacture or treatment of nanostructures, more specifically to the field of nanostructures for the release of hydrophobic compounds.

TECHNICAL STATE

Nanotechnology has been experiencing rapid growth with several innovative applications in the pharmaceutical, cosmetic, food, chemical, materials science and polymer industry. In the pharmaceutical area, nanostructured systems such as nanoparticles, liposomes, nanoemulsion and dendrimers have emerged in recent decades as carrier systems of hydrophobic compounds.

For these compounds, poor water solubility is the limiting factor for their use in different applications in the pharmaceutical, cosmetic and food industry.

The development of new nanostructured release systems represents an efficient strategy for the delivery of hydrophobic compounds. The choice of these systems enables the solubilization of these assets and, consequently, an increase in their effectiveness and tolerability. Also, in the case of drugs, the specificity and the decrease of the dose amount in these new systems reduce their adverse effects.

In this context, hydrophobic compounds may be administered as emulsions, wherein the substance is dissolved in an organic solvent, which is dispersed in an aqueous phase as droplets and stabilized with a surfactant, the colloidal stability of these formulations being controlled by the chemical structure of the formulation. interface. In this field, nanoemulsions have been studied and the interest in their application owes to the ability of these systems to increase the solubility and hence the bioavailability of hydrophobic assets; the ability to incorporate hydrophilic and hydrophobic actives at the same time and improving their stability.

Nanostructured systems have a size range from 1 to 999 nm. However, as compound release systems, the nano effect is only evident for systems in the range of 20 to 200 nm where high permeability of these systems in biological membranes and cells is achieved.

Since the size of the nanoemulsion droplets is less than Ιμιη, smaller than the diameter of the 4 μπι blood capillaries, nanoemulsions can be administered intravenously as well as intramuscularly and subcutaneously, thereby minimizing health risks. In addition, parenterally administered drugs directly affect the systemic circulation, preventing the first-pass effect caused by hepatic metabolism.

Considering the potentialities of nanoemulsion systems in the administration of poorly soluble compounds, enabling the delivery of a drug, such as praziquantel in nanoemulsions may be an interesting strategy for the development of an emulsified pharmaceutical form for oral use and in the future it may also be applied for parenteral use, which to date are not commercially available. This drug belongs to the broad spectrum anthelmintics class and is of first choice for the treatment of schistosomiasis.

As another example, the elaboration of nanoemulsions containing photosensitizing agents may be cited. Zinc Phthalocyanine (PhyZn) and Chloro-Aluminum Phthalocyanine (PhyAl) to improve the bioavailability of these drugs. Phthalocyanines are second generation photosensitizing drugs that are currently used in photodynamic therapy (PDT) in cancer treatment.

In addition, the delivery of fat-soluble vitamins in nanoemulsified systems such as vitamin E may be of particular interest to the cosmetic industry.

PURPOSE OF THE INVENTION

The present invention relates to a nanoemulsion containing at least one surfactant, an oil and optionally a solvent. The invention also relates to the process of producing a nanoemulsion containing at least one hydrophobic compound, at least one surfactant, an oil and optionally a solvent.

BRIEF DESCRIPTION OF DRAWINGS

In order to obtain a full view of the objects of the present invention, it is necessary to read this document and analyze the accompanying drawings to which reference is made as follows.

FIGURE 1 shows the droplet size chart of the nanoemulsion containing 5% of clove essential oil, relative to preparation time.

FIGURE 2 shows the droplet size chart of the nanoemulsion containing the clove essential oil and praziquantel drug relative to preparation time.

FIGURE 3 shows the droplet size graphs of nanoemulsion containing clove essential oil, ZN and Cl-Al phthalocyanine, relative to preparation time.

Figure 4 shows the droplet size chart of nanoemulsion containing clove essential oil and vitamin E, relative to preparation time. Figure 5 shows the graph of the nanoemulsion toxicological profile, containing clove essential oil and praziquantel drug, on viability of Caco-2 cells after 5 and 24h incubation.

Figure 6 shows the different systems tested in the transport study through Caco-2 cells. (■) ethanol-soluble praziquantel dispersed in N- (2-hydroxyethyl) piperazine- '- (2-ethanesulfonic acid) (HEPES) at the concentration of ΙΟΟμΜ; (♦) Orange oil nanoemulsion containing praziquantel, 1.25mg / mL in HBSS; (A) Clove oil nanoemulsion containing praziquantel, 5 mg / mL in HBSS; () PRAZIQUANTEL-containing PLGA nanoparticles, 0.1 mg / mL in HBSS.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is an oil in water nanoemulsion consisting of at least one surfactant, at least one oil and optionally one or more solvents.

The nanoemulsion contains from 5 to 40% mass / mass (w / w) of a nonionic surfactant known to those skilled in the pharmaceutical field, such as surfactants in the group consisting of: poly (ethylene oxide) block copolymers ) -poly (propylene oxide) (PEO-PPO) or ethoxylated alcohols or a mixture thereof.

Preferably, the nanoemulsion comprises from 7 to 25% w / w of a nonionic surfactant or mixtures of nonionic surfactants.

The oil phase consists of from 1 to 50% w / w of a vegetable oil, which may be a crude oil and / or an essential oil. The essential oils that may be used in this invention are, for example, the essential oil of: lemongrass (Cymbopogon citratus), orange (Citrus sinensis), clove (Eugenia caryophyllus), lime {Citrus. aurantifolia), lemon balm (Melissa offícinalis), passion fruit (Passiflora spp), mint (Mentha spp) and / or a mixture of these essential oils.

Crude oils which may be used in this invention are, for example, oils belonging to the group consisting of: avocado (Persea gratissima), fennel (Foeniculum vulgare), rapeseed (Brassica napus), buriti (Mauritia flexuosa), almond ( Prunus dulcis), grape seed (Vitis spp), and / or a mixture of these crude oils. Optionally a mixture between an essential oil and a crude oil may also be used.

Preferably, between 2.5 and 20% of orange essential oil (Citrus sinensis), clove (Eugenia caryophyllus), lime (Citrus. Aurantifolia), and / or lemon balm (Melissa offícinalis) is employed. Most preferably, the oil is the essential orange (Citrus sinensis) and / or clove.

The nanoemulsion further contains one or more hydrophobic compounds in the ratio of 0.5: 1 to 1/20 m / m. Hydrophobic compounds are those that have little or no water solubility, and the solubilization of these compounds enables the production of liquid formulations for use, for example, topical, oral or parenteral.

In this invention, hydrophobic compounds may be poorly soluble or water-insoluble drugs such as carbamazepine, dapsone, griseofulvin, ibuprofen, nifedipine, nitrofurantoin, phenytoin, sulfamethoxazole, trimethoprim, acid. valproic acid, iopanoic acid, nalidixic acid, nevirappine, rifampicin, amitriptyline, aluminum hydroxide, furosemide, indinavir, nelfinavir, ritonavir, saquinavir, acetazolamide, azathioprine, albendazole, lumetfantrine, artemether, chlorpromazine, chlorpromazine, chlorpromazine, , glibenclamide, haloperidol, ivermectin, lopinavir, mebendazole, mefloquine, niclosamide, pyrantel, pyrimethamine, spironolactone, sulfadiazine, sulfasalazine, triclabendazole, zinc phthalocyanine and chloroaluminum phthalocyanine. Also, fat-soluble vitamins such as retinol, beta-carotene, tretinoin, alfacarotene, ergocalciferol, cholecalciferol, didrotaquisterol, calcitriol, calcidiol, tocopherol, tocotrienol, naphthoquinone, phylloquinone and menatetrenone. Also possible are cosmetics such as, for example, octyl methoxycinnamate (MCO) and also fat soluble food products.

Preferably, the hydrophobic compound is: praziquantel, zinc phthalocyanine, chloroaluminum phthalocyanine, tocopherol or tocotriene.

Optionally, approximately 30% of one or more solvents may be used to compose the oil phase and increase the solubility of hydrophobic compounds. The solvents that may be used are alcohols, such as ethanol and glycerol.

The nanoemulsion of this invention has an average diameter of 1 to 200 nm, preferably 5 to 100 nm.

The invention further relates to the process of producing an oil-in-water nanoemulsion comprising the steps of:

(a) dissolving one or more surfactants in water;

(b) Preparation of the oil phase;

(c) Mixture of aqueous and oily phases.

Step (a) begins by adding from 5 to 40% mass / mass (w / w) of a nonionic surfactant in water. The surfactants employed in this invention belong to the group consisting of poly (ethylene oxide) -poly (propylene oxide) block copolymers (PEO-PPO); ethoxylated alcohols; or a mixture thereof. Then the surfactant solution in water is allowed to stand at room temperature. 5 ° C for a period of 12 hours for complete solubilization.

The oil phase (b) consists of a vegetable oil, which may be a crude oil and / or an essential oil. The essential oils that can be used in this invention are, for example, the essential oils of: lemongrass (Cymbopogon citratus), orange (Citrus sinensis), clove (Eugenia caryophyllus), lime (Citrus aurantifolia), lemon balm { Melissa officinalis), passion fruit (Passiflora spp), mint (Mentha spp) and / or a mixture of these essential oils.

Crude oils which may be used in this invention are, for example, the oils of: avocado (Persea gratissima), fennel (Foeniculum vulgare), rapeseed (Brassica napus), buriti (Mauritia flexuosa), almond (Prunus dulcis), grape seed (Vitis spp), and / or a mixture of these crude oils.

Preferably, the essential oil of orange (Citrus sinensis), clove (Eugenia caryophyllus), lime (Citrus. Aurantifolia), and / or lemon balm (Melissa officinalis) is used. Most preferably, the oil is the essential orange (Citrus sinensis) and / or clove.

To the oil phase, one or more hydrophobic compounds in the ratio of 0.5: 1 to 1/20 m / m are added under stirring over a period of up to 10 minutes.

Hydrophobic compounds have little or no water solubility. These compounds are also known as hydrophobic or supportive, lipophilic or fat soluble. Moreover, their solubilization enables the production of liquid formulations for use, for example, topical, oral or parenteral. Hydrophobic compounds may be poorly soluble or water-insoluble drugs, such as carbamazepine, dapsone, griseofulvin, ibuprofen, nifedipine, nitrofurantoin, phenytoin, sulfamethoxazole, trimethoprim, valproic acid, iopanoic acid, nalidixin, rifipin, hydriphoxine, rifampine, aluminum, furosemide, indinavir, nelfinavir, ritonavir, saquinavir, acetazolamide, azathioprine, albendazole, lumetfantrine, artemether, chlorpromazine, ciprofloxacin, clofazimine, efavirenz, diloxanide, folic acid, glibenclamide, meoperidine, haloperidine pyrimethamine, spironolactone, sulfadiazine, sulfasalazine, triclabendazole, zinc phthalocyanine and chloroaluminum phthalocyanine. In addition, fat-soluble vitamins such as retinol, beta-carotene, tretinoin, alfacarotene, ergocalciferol, cholecalciferol, didrotaquisterol, calcitriol, calcidiol, tocopherol, tocotrienol, naphthoquinone, phylloquinone and menatetrenone. Also possible are cosmetics such as, for example, octyl methoxycinnamate (MCO) and also fat soluble food products.

Preferably, the hydrophobic compound employed is praziquantel, zinc phthalocyanine, chloroaluminum phthalocyanine, tocopherol or tocotriene.

Optionally, one or more solvents may be used to compose the oil phase and increase the solubility of hydrophobic compounds. The solvents that may be used are alcohols, such as ethanol and glycerol.

The oil phase composed of an oil or mixtures of oils, hydrophobic compounds and optionally one or more solvents is mixed with the aqueous phase in the oil phase proportions between 0.5 / 1 (0.5%) to 1/5 ( 20%) v / v. After mixing the two phases it is homogenized in high energy equipment for vigorous homogenization for 1 to 15 minutes; between 5 and 35 ° C; can occur at positive pressure up to 125 MPa, so that an O / W nanoemulsion in the form of droplets is obtained.

The O / W nanoemulsion thus obtained occurs as gauge droplets, the mean diameter of which according to the above steps is from 1 to 200 nm, preferably from 5 to 10.0 nm.

The homogenization equipment used in this step is state of the art and may, for example, be high pressure (PAH) or ultrasound (US) equipment.

The Nanoemulsion objects of this invention allow an increase in the therapeutic index of hydrophobic compounds, as well as minor side effects and prolonged therapeutic effect, since the compound is solubilized in an oil phase, which in turn is dispersed in water in the form of nanogoticles.

In addition, Nanoemulsions may be used for the delivery of other hydrophobic compounds, such as fat-soluble vitamins, antioxidants used by the cosmetic, food and pharmaceutical industries.

Although the invention has been widely described, it is obvious to those skilled in the art that various changes and modifications may be made without such changes being covered by the scope of the invention.

The examples below are merely intended to illustrate embodiments of the present invention, and are not intended to restrict or delimit the rights of the proprietor, which should only be limited to the scope of the claims set forth.

Examples: 0023

Example 1: Nanoemulsion containing praziquantel drug (solubility study):

Praziquantel was subjected to solubility tests on different oils at concentrations of 1-30% w / v. The following oils were used: almonds, grape seed, avocado, sweet fennel, almond, lipo S, buriti, isopropyl myristate, octyl palmitate and essential oils such as cloves, lime, mint, passion fruit, lemongrass, Lemon balm and orange. The choice of the oil phase for the preparation of nanoemulsions was made by visual observation using a qualitative criterion based on the United States Pharmacopoeia (USP) in the chapter entitled "Description and Relative Solubility" (USP, 1995).

Example 2: Preparation of Nanoemulsions containing (or not) the praziquantel drug in orange or clove essential oil.

Oil-in-water nanoemulsions were prepared by the high energy method, in ultrasound (US) or in high pressure homogenizer. The oily phase consisted (or not) of praziquantel dissolved in the orange or clove essential oil at a concentration of 5% w / w of the formulation. For the formation of these Nanoemulsions a commercial ethoxylated alcohol based or PEO-PPO block copolymer surfactant was used, which were employed at a concentration of 12% w / w.

Nanoemulsions prepared (whether or not containing) the drug showed good stability and droplet sizes below 100 nm.

Example 3: Nanoemulsion containing phthalocyanine-based drugs (solubility study).

Zinc phthalocyanine (PhyZn) was dissolved in several types of essential oils, measuring the volume of oil needed to solubilize 1mg of the drug. Every 1 mL of After the oil was added, the sample was ultrasounded and then evaluated for the presence of insoluble particles in the sample. This procedure was repeated until the solution was clear, no trace of unsubstituted drug, or 10mL of oil was spent. In addition to the oils, the test was also performed with DMSO in order to prove PhyZn solubility in it. The results obtained are described in Table 1.

Table 1: Solubility of zinc phthalocyanine in different types of oils.

To characterize the incorporation of the drug into the oil, UV spectrometry analyzes were performed, observing between 600 - 750nm the characteristic peak of phthalocyanine.

The solubility of the chloraluminum phthalocyanine (PhyAl) drug was also evaluated in these different oils, being even more soluble in the presence of the ethanol solvent.

Example 4: Preparation of Nanoemulsions containing (or not) phthalocyanine-based drugs in clove essential oil (whether or not containing solvents).

Three oil phases proved to be good candidates for the development of phthalokinan-containing nanoemulsion: PhyZn clove oil; Clove Oil with PhyAl and Clove Oil with PhyAl and Ethanol.

A PEO-PPO block copolymer was used in the Nanoemulsion preparation. These were prepared in a high pressure homogenizer (PAH) using surfactant amounts of 10 and 12% and 5, 7, 10 and 15% of each of the oil phases. The obtained nanoemulsions were clear and with small droplet size. In addition, formulations containing ethanol in the oil phase showed even better results, achieving Nanoemulsion with up to 10% oil phase, suggesting that ethanol acts as a co-surfactant in the formulation.

Example 5: Nanoemulsion Stability Study

The stability of o / w Nanoemulsions, obtained in the presence or not of hydrophobic compounds, was evaluated for the size distribution of the droplets formed as a function of time after preparation, in order to follow the variation of the size distribution of the dispersed droplets and, if so, destabilization of these emulsions.

This evaluation was performed by initially analyzing the size distribution of the emulsion dispersed particles at time zero. Then, the emulsion was allowed to stand and further analyzes were performed from time to time until the phase separation of these systems was observed.

The study was performed on a particle size analyzer, all analyzes being performed in triplicate. Therefore, the graphs obtained show the average particle size distribution curves of the emulsions, with their error bars.

The average diameter of these particles is shown in the graphs shown in Figures 1 to 4.

Table 2 shows some of the Nanoemulsions obtained with the aid of US equipment.

Table 3 shows some of the Nanoemulsions obtained with the aid of HAP equipment.

Table 2: Nanoemulsions prepared in PAH equipment.

Example 6: Study of the toxicological profile of formulations containing praziquantel in Caco-2 cells.

The cytotoxicity of two formulations presented in this work, one containing orange oil and the other containing clove oil, praziquantel% and PEO- block copolymer PPO was evaluated by measuring the viability of Caco-2 cells in the presence and absence of formulations. The method used in this study used the reagent 3- (4, 5-dihydro ^{'methylthiazol-2-yl)} -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium (MTS), which measures mitochondrial activity of cells. Caco-2 cells were cultured in 96-well plates containing 250,000 cells / cm ² for 72 hours. After this period, the culture medium was removed from each well. The different formulations were diluted in culture medium and added to each well, cells were incubated in this medium for 5 and 24 hours at 37 ° C with 95% relative humidity and 5% CO _∑ . After this incubation time, 20 µl of MTS solution (5 mg / ml) was added to each well and again incubated for 3 hours under the same conditions as above. The absorbance of each well was made by spectroscopic measurements at 530 nm. Cytotoxicity was expressed as a percentage of cell viability, which is calculated by the ratio between the number of cells treated (addition of different formulations) and control cells (culture medium only).

From the results obtained it was possible to determine the cytotoxicity of formulations containing Nanoemulsion. More preferably the nanoemulsions containing the orange essential oil soluble praziquantel drug and the blackhead essential oil soluble praziquantel (Figure 5). Example 7: Formulation Transport Study

Four different systems were used to evaluate the absorption rate of PRAZIQUANTEL in Caco-2 cells.

Figure 6 shows the different systems tested in the transport study through Caco-2 cells.

After 21 days of cultivation, Caco-2 cells were incubated with the respective systems in the apical region, in the basolateral region, pH 7.4 HEPES was added. The sign It was kept in an oven at 37 ° C and after 15, 45, 90 and 120 minutes the entire volume of the basolateral region was removed with immediate replacement of the same volume of DMEM with pH 7.4. At the end of 120 minutes, the cells were washed with Hank's Balanced Solution (HBSS) and then 0.2 mL of DMEM was added to the apical region and the cells incubated for a further 22 hours. The content was determined by high performance liquid chromatography.

The results indicate that the nanostructured systems presented a higher efficiency in the permeability of the drug PRAZIQUANTEL compared to the free drug in ethanol solution.

Example 8: Phototoxicity Study of Formulations

Toxicity and phototoxicity studies were performed for Nanoemulsions containing chloroaluminium photalocyanine using A549 lung adenocarcinoma cells. These trials aim to evaluate the toxic potential of formulations and their separate components. For this The study was divided into two stages: one in the dark (Toxicity Study) and one in the light (Phototoxicity Study). Initially, the cells are distributed in a plate containing 96 wells. It is incubated in an oven at 37 ° C for a period of 24 hours so that the cells can adhere to the bottom of the well. Then different solutions composed of: drug nanoemulsion, drugless nanoemulsion, ethanol drug control and saline only control are added to the wells separately. After addition of the solutions, the plates are incubated again for 24 hours. After this time, the phototoxicity test plate is red-lighted and returned to the oven for a further 24 hours, while the toxicity test plate is kept in the oven. Finally, both Plates are removed from the greenhouse for counting the number of viable cells by the 3- (4,5-dimethylthiazol-2-yl) 2-5-differed tetrazolium (MTT) method. Phthalocyanine - containing nanoemulsions were found to have phototoxic activity, while the other components did not show phototoxicity when compared to the control. Toxicity assay showed slight toxicity of nanoemulsion containing Chloroaluminium Phthalocyanine when compared to control, but not significant when compared to phototoxicity assay.

Claims

1 - Oil-in-water nanoemulsion characterized in that it consists of 5 to 40% mass / mass (w / w) of at least one surfactant, between 1 to 50% w / w of at least one oil; and optionally approximately 30% of one or more solvents.

Nanoemulsion according to Claim 1, characterized in that it contains a nonionic surfactant belonging to the group consisting of poly (ethylene oxide) -poly (propylene oxide) block copolymers (PEO-PPO); ethoxylated alcohols; or a mixture thereof.

Nanoemulsion according to Claim 2, characterized in that it comprises from 7 to 25% w / w of a nonionic surfactant or mixtures of nonionic surfactants.

Nanoemulsion according to Claim 1, characterized in that the oil phase consists of 1 to 50% w / w of a vegetable oil, which may be a crude oil and / or an essential oil.

Nanoemulsion according to Claim 4, characterized by the essential oil of: lemongrass (Cymbopogon citratus), orange (Citrus sinensis), clove (Eugenia caryophyllus), lime (Citrus aurantifolia), lemon balm (Melissa officinalis) , passion fruit (Passiflora spp), mint (Mentha spp) and / or a mixture of these essential oils.

Nanoemulsion according to claim 4, characterized by crude oil belonging to the group consisting of: avocado (Persea gratissima), fennel (Foeniculum vulgare), rapeseed (Brassica napus), buriti (Mauritia flexuosa), almond (Prunus dulcis ), grape seed (Vitis spp), and / or a mixture of these crude oils.

Nanoemulsion according to any one of claims 1, 4, 5 and 6, characterized in that it employs between 2.5 and 20% orange essential oil (Citrus synensis), cloves (Eugenia caryophyllus), lime (Citrus. aurantifolia), and / or lemon balm (Melissa officinalis).

Nanoemulsion according to Claim 1, characterized in that it contains one or more hydrophobic compounds belonging to the group consisting of: carbamazepine, dapsone, griseofulvin, ibuprofen, nifedipine, nitrofurantoin, phenytoin, sulfamethoxazole, trimethoprim, valproic acid, nopanoic acid, nopanoic acid , nevirappine, rifampicin, amitriptyline, aluminum hydroxide, furosemide, indinavir, nelfinavir, ritonavir, saquinavir, acetazolamide, azathioprine, albendazole, lumetfantrine, artemether, chlorpromazine, ciprofloxacin, clofazenzine, haloperidine, glofazenzine, efaviride lopinavir, mebendazole, mefloquine, niclosamide, praziquantel, pirantel, pyrimethamine, spironolactone, sulfadiazine, sulfasalazine, triclabendazole, zinc phthalocyanine and chloroaluminum phthalocyanine. Further, fat-soluble vitamins such as retinol, beta-carotene, tretinoin, alpha-carotene, ergocalciferol, cholecalciferol, didrotaquisterol, calcitriol, calcidiol, tocopherol, tocotrienol, naphthoquinone, phylloquinone and menatetrenone; in the ratio of 0.5: 1 to 1/20 m / m.

Nanoemulsion according to claim 1, characterized in that approximately 30% of a solvent is optionally used.

Nanoemulsion according to Claim 1, characterized in that it has an average diameter of 5 to 100 nm.

A process for producing an oil-in-water nanoemulsion comprising the steps of:

(a) dissolving one or more surfactants in water;

(b) Preparation of the oil phase;

(c) Mixture of aqueous and oily phases. Production process according to Claim 10, characterized in that the step (a) begins by adding from 5 to 40% mass / mass (w / w) of a nonionic surfactant belonging to the group consisting of block copolymers. poly (ethylene oxide) poly (propylene oxide) (PEO-PPO); ethoxylated alcohols; or a mixture thereof in water.

Production process according to Claim 11, characterized in that step (a) leaves the surfactant solution in water at rest at 5 ° C for a period of 12 hours for complete solubilization.

Production process according to Claim 10, characterized in that the oil phase (b) consists of a vegetable oil, which may be a crude oil and / or an essential oil.

Production process according to Claim 10, characterized in that it adds one or more hydrophobic compounds in the ratio of 0.5: 1 to 1/20 m / m under stirring over a period of up to 10 minutes.

Production process according to Claim 14, characterized in that the hydrophobic compounds are praziquantel, zinc phthalocyanine, chloroaluminum phthalocyanine, tocopherol or tocotriene.

Production process according to Claim 10, characterized in that one or more solvents may optionally be used.

Production process according to Claim 10, characterized in that the oil phase is mixed with the aqueous phase in the oil phase proportions between 0.5 / 1 (0.5%) and 1/5 (20%) v / v. by vigorous homogenization for 1 to 15 minutes; 5 to 35 ° C and can occur at positive pressure up to 125 MPa, so that an O / W nanoemulsion in the form of droplets is obtained. 18 - Use of a nanoemul: are oil in water consisting of 5 to 40% mass / mass (w / w) of at least one surfactant, between 1 to 50% w / w of at least one oil; and optionally approximately 30% of one or more solvents, characterized in that it is for the delivery of hydrophobic compounds, which may be a drug, cosmetic, vitamin or a food compound.