[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2016097011A1 - Composition pharmaceutique comprenant de l'agomélatine amorphe - Google Patents

Composition pharmaceutique comprenant de l'agomélatine amorphe Download PDF

Info

Publication number
WO2016097011A1
WO2016097011A1 PCT/EP2015/080039 EP2015080039W WO2016097011A1 WO 2016097011 A1 WO2016097011 A1 WO 2016097011A1 EP 2015080039 W EP2015080039 W EP 2015080039W WO 2016097011 A1 WO2016097011 A1 WO 2016097011A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclodextrin
nilotinib
pharmaceutically acceptable
composition according
solvent
Prior art date
Application number
PCT/EP2015/080039
Other languages
English (en)
Inventor
Rolf Keltjens
Raymond Jozef Hubertus Westheim
Deepak Murpani
Original Assignee
Synthon B.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synthon B.V. filed Critical Synthon B.V.
Publication of WO2016097011A1 publication Critical patent/WO2016097011A1/fr

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1652Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin

Definitions

  • Nilotinib chemically 4-methyl-N-[3-(4-methyl-l-H-imidazol-l-yl)- 5- (trifluoromethyl)phenyl]-3- [(4-pyridin-3-ylpyrimidin-2-yl) amino ]benzamide of formula (I),
  • the compound was discovered by Novartis and was first described in WO2004005281.
  • the compound may form acid addition salts, for instance Nilotinib hydrochloride, which is the active ingredient in the medicinal product sold under the brand name Tasigna ® 150 and 200 mg capsules by Novartis.
  • Nilotinib monohydrochloride monohydrate is described in WO2007015871.
  • Nilotinib hydrochloride shows a complex solid state behaviour with numerous forms (anhydrates, hydrate, solvates) and with a very low aqueous solubility leading to a poor bioavailability.
  • Several patent applications provide salts and polymorphs of Nilotinib aiming to improve its solubility.
  • WO2007015870 describes several polymorphs of Nilotinib hydrochloride, their process of preparation and compositions comprising them. Crystalline form B of the hydrochloride salt is a monohydrate which has a theoretical moisture content of 3.1% and was described as showing superior crystalline and physical stability with respect to form A of the hydrochloride salt.
  • WO2007015870 additionally describes amorphous Nilotinib hydrochloride.
  • amorphous Nilotinib hydrochloride spontaneously converts to the form A hydrochloride salt after storage at various relative humidities.
  • amorphous Nilotinib hydrochloride as such is unstable, hygroscopic and not suitable for use on pharmaceutical production scale.
  • Nilotinib showing an appropriate solubility/dissolution rate and which is simple to prepare, suitable for use on a commercial scale stable in time also within the pharmaceutical composition.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising an inclusion complex of Nilotinib, or a pharmaceutically acceptable salt thereof, in amorphous form in a cyclodextrin and one or more pharmaceutically acceptable excipients.
  • It also provides a process for preparing said inclusion complex by dissolving Nilotinib, or a pharmaceutically acceptable salt thereof, and a cyclodextrin in a suitable solvent or solvent mixture, followed by evaporation of the solvent(s), and the pharmaceutical composition obtainable by such process.
  • Said pharmaceutical composition may be used as a medicament, particularly in the treatment of Philadelphia-chromosome-positive chronic myelogenous leukaemia. DETAILED DESCRIPTION OF THE PRESENT INVENTION
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising an inclusion complex of Nilotinib, or a pharmaceutically acceptable salt thereof, in amorphous form in cyclodextrin and one or more pharmaceutically acceptable excipients.
  • Cyclodextrins are compounds made up of sugar molecules bound together in a ring and are composed of 5 or more a-D-glucopyranoside units linked 1 ⁇ 4. Cyclodextrins are produced from starch by means of enzymatic conversion. Three major non-substituted cyclodextrins are known, containing each a different number of glucose monomers ranging from six to eight in a ring, creating a conical shape. The so-called a-cyclodextrin is a six- membered sugar ring molecule, ⁇ -cyclodextrin is a seven- membered sugar ring molecule and ⁇ -cyclodextrin is an eight-membered sugar ring molecule.
  • ⁇ -cyclodextrins exhibits poor water solubility.
  • various semi synthetic derivatives with enhanced aqueous solubility have been developed.
  • Well known examples are Sulfobutylether ⁇ -cyclodextrin sodium salt, which is a partially substituted ⁇ -cyclodextrin. Its aqueous solubility is high, exceeding 500 mg/ml and 2 hydro xypropyl ⁇ -cyclodextrin with a solubility exceeding 600 mg/ml.
  • Cyclodextrins may form complexes with various chemicals (guest molecules), in which the chemical is encapsulated inside the cyclodextrin ring and forms a so called inclusion complex.
  • guest molecules chemical molecules
  • the chemical is encapsulated inside the cyclodextrin ring and forms a so called inclusion complex.
  • original properties of the compound vis-a-vis the cyclodextrin-complexed compound may be modified (Arthur H. Kibbe (Ed.), Handbook of Pharmaceutical Excipients, Third Edition 2000, p. 165-168).
  • Drugs that can exist in either amorphous or crystalline form tend to crystallize over time when present in amorphous state because the crystalline form of the drug is a lower- energy state than the amorphous form.
  • Active Pharmaceutical Ingredients may form inclusion complexes in cyclodextrins wherein the API in the inclusion complex is kept in amorphous form (Thorstein Loftsson at al., Pharmaceutical Sciences, 85(10), 1996, 1017- 1025). It is however not self-evident that a given drug will form an inclusion complex with just any cyclodextrin, and that, even in the event the complex is formed, it will be stable over time.
  • Factors playing a role herein are the physicochemical properties of both API and cyclodextrin, the ratio of API to cyclodextrin used, the technique used to prepare the complex and in the solvent evaporation techniques, the speed of solvent evaporation where a higher evaporation speed leads to a higher probability of isolating amorphous material.
  • cyclodextrin complexation procedures are relatively simple processes, these techniques often require very specific conditions for each guest molecule (John L. Koontz et al., J. Agric. Food Chem., 57(4), 2009, p. 1162-1171).
  • the inclusion complex of the current invention is very stable at such weight ratios of nilotinib or its salt thereof in relation to cyclodextrin such that nilotinib or its salt thereof, is present in clear molecular excess. Even at a weight ratio of nilotinib, or a pharmaceutically acceptable salt thereof, to cyclodextrin as low as 1: 1 the stability of the pharmaceutical composition is not decreasing. During stability studies no conversion into any crystalline form was observed for such compositions, even under stress conditions. With regard to impurity levels, also no significant differences have been observed. The
  • composition shows sufficient long term stability.
  • nilotinib, or a pharmaceutically acceptable salt thereof in amorphous form in a cyclodextrin, wherein nilotinib, or a pharmaceutically acceptable salt thereof, is present in such molecular excess, can not only be explained for by (partial) encapsulation of nilotinib, or a pharmaceutically acceptable salt thereof, in the cyclodextrin cavity.
  • Nilotinib, or a pharmaceutical acceptable salt thereof is also accommodated in the intermolecular cavities formed or sandwich-like between layers of cyclodextrin. As described by Jozsef Szejtli (Cyclodextrin Technology, 1988, p.
  • the "intercalation" enhances the molar ratio in favour of the guest molecule, which could account for that, although nilotinib, or a pharmaceutically acceptable salt thereof, is present in molar excess amounts over the cyclodextrin, the stability of the pharmaceutical compositions is still excellent.
  • compositions prepared with the inclusion complex display dissolution behaviour typical for immediate-release formulations.
  • the compositions of the present invention exhibit a dissolution rate of at least 80% in 30 minutes when tested in 1000 ml of 0.1 N HC1 in a USP apparatus I (basket) at 100 rpm.
  • compositions of the present invention behaved similar to Tasigna ® in the above mentioned dissolution test.
  • the weight ratio of nilotinib, or a pharmaceutically acceptable salt thereof, to cyclodextrin in the inclusion complex ranges from about 1: 1 to about 1:4 and is preferably 1:2.5.
  • ⁇ -Cyclodextrin is the cheapest cyclodextrin, regarded as a safe compound and is widely applied in food and pharmaceutical industry.
  • At least a major portion of nilotinib, or a pharmaceutically acceptable salt thereof, in the inclusion complex is amorphous.
  • the term "a major portion" of nilotinib, or a pharmaceutically acceptable salt thereof, in the inclusion complex is amorphous.
  • nilotinib, or a pharmaceutically acceptable salt thereof, in the inclusion complex is in a completely amorphous form within the detection limits of the techniques used for characterization.
  • the inclusion complex in accordance with the present invention advantageously is in the form of a free-flowing powder, with excellent handling properties and stable morphology.
  • the inclusion complex is very suitable to be used for the preparation of pharmaceutical compositions.
  • the pharmaceutical compositions of the present invention comprise the inclusion complex of nilotinib, or a pharmaceutically acceptable salt thereof, in cyclodextrin and one or more pharmaceutically acceptable excipients.
  • the excipients to be used in accordance with the present invention are well-known and are those excipients which are conventionally used by the person skilled in the art. Depending on the dosage form chosen for the pharmaceutical composition, the person skilled in the art will be able to select suitable pharmaceutically acceptable excipients.
  • the dosage form is a capsule or an immediate release tablet and the pharmaceutically acceptable excipients are chosen from one or more binders, diluents, disintegrants, glidants, lubricants, stabilizers, surface active agents or pH-adjusting agents. More preferably, the composition of the present invention comprises a diluent, a disintegrant and a lubricant.
  • the diluent to be used in accordance with the present invention may be any diluent known to a person of ordinary skill in the art.
  • the diluent to be used in accordance with the present invention is an inorganic diluent, polysaccharide, mono- or disaccharide or sugar alcohol.
  • Microcrystalline cellulose is a particularly preferred diluent.
  • the disintegrant to be used in accordance with the present invention may be any disintegrant known to a person of ordinary skill in the art. Suitable disintegrants to be used in accordance with the present invention are selected from the group consisting of
  • Croscarmellose sodium is a particularly preferred disintegrant.
  • the lubricant to be used in accordance with the present invention may be any lubricant known to a person of ordinary skill in the art.
  • Magnesium stearate is a particularly preferred lubricant.
  • At least one of the pharmaceutically acceptable excipients is an intragranular excipient.
  • the intragranular excipient to be used in accordance with the present invention is a diluent.
  • Microcrystalline cellulose is a particularly preferred diluent.
  • At least one of the pharmaceutically acceptable excipients is an extragranular excipient.
  • the extragranular excipient is chosen from one or more diluents, disintegrants and lubricants. More preferably, the extragranular excipient to be used in accordance with the present invention is a disintegrant.
  • Croscarmellose sodium is a particularly preferred disintegrant.
  • the diluent microcrystalline cellulose and the lubricant magnesium stearate may be used as extragranular excipients.
  • the intragranular excipient is microcrystalline cellulose and the extragranular excipients are microcrystalline cellulose, croscarmellose sodium and magnesium stearate.
  • compositions of the present invention display dissolution behaviour typical for immediate-release formulations, exhibiting a dissolution rate of at least 80% in 30 minutes when tested in 1000 ml of 0.1 N HC1 in a USP apparatus I (basket) at 100 rpm.
  • nilotinib or a pharmaceutically acceptable salt thereof, remains in the amorphous form.
  • the present invention further provides a process to prepare an inclusion complex of nilotinib, or a pharmaceutically acceptable salt thereof, in cyclodextrin, comprising dissolving the cyclodextrin and nilotinib, or a pharmaceutically acceptable salt thereof, in a suitable solvent or solvent mixture, followed by evaporation of the solvent(s), using equipment and methods well-known in the art.
  • the solvent or solvent mixture is water, a dilute aqueous acid, a polar organic solvent or a mixture of water/dilute aqueous acid and a polar organic solvent.
  • the process of the current invention may be performed at elevated temperatures in order to dissolve the cyclodextrin completely.
  • the mixture of ⁇ -cyclodextrin and solvent(s) is heated to temperatures ranging from 40°C to reflux.
  • the cyclodextrin is dissolved in water or a mixture of water and a polar organic solvent by heating and nilotinib, or a pharmaceutically acceptable salt thereof, is added to this solution.
  • Preferred polar organic solvents are alcohols, particularly ethanol or methanol, ethers, particularly
  • the inclusion complex is prepared by dissolving cyclodextrin in water by heating, followed by the addition of nilotinib
  • the present invention further provides an inclusion complex of nilotinib, or a pharmaceutically acceptable salt thereof, in cyclodextrin, exhibiting a dissolution rate of at least 80% in 30 minutes when tested in 1000 ml of 0.1 N HCl in a USP apparatus I (basket) at 100 rpm., obtainable by:
  • the pharmaceutically acceptable salt of nilotinib herein is the hydrochloric acid salt and the solvent is water/ethanol or dilute aqueous acid/ethanol.
  • the present invention still further provides a process to prepare pharmaceutical compositions comprising an inclusion complex of nilotinib, or a pharmaceutically acceptable salt thereof, in cyclodextrin and one or more pharmaceutically acceptable excipients.
  • the process comprises mixing or granulating the inclusion complex with one or more
  • nilotinib or a pharmaceutically acceptable salt thereof, and the cyclodextrin was sprayed over a diluent in a fluidized bed and the resulting granulate/blend was mixed with one or more pharmaceutically acceptable extragranular excipients, followed by encapsulation.
  • HPMC or gelatin capsules are used.
  • nilotinib hydrochloride and cyclodextrin in water/acetone was sprayed over lactose in a fluidized bed, after which the granulate/powder blend was mixed with microcrystalline cellulose and magnesium stearate, followed by filling into capsules.
  • the pharmaceutical compositions of the present invention are packaged in blister pack material.
  • the blister pack materials to be used in accordance with the present invention may be any blister pack material known to a person of ordinary skill in the art. Suitable blister pack materials to be used in accordance with the present invention are selected from the group of PVC/Alu, Duplex/ Alu, Trip lex/ Alu and Alu/Alu. To ensure protection of the compositions of the present invention from e.g. moisture and thereby preventing polymorphic conversions, Triplex/ Alu and Alu/Alu are particularly preferred blister pack materials. After storage of the pharmaceutical compositions in these blister pack materials for 6 months at 40°C/75 RH, XRPD analysis showed no reflections in accordance with crystalline nilotinib hydrochloride.
  • the pharmaceutical composition in accordance with the present invention may be used as a medicament.
  • the pharmaceutical composition typically may be used in the treatment of Philadelphia-chromosome-positive chronic myelogenous leukaemia.
  • the following examples are intended to illustrate the scope of the present invention but not to limit it thereto.
  • Example 1 inclusion complex of amorphous nilotinib hydrochloride : sulfo butyl ether ⁇ -cyclodextrin (weight ratio 1:3)
  • Nilotinib HC1 and 1.5 g of sulfo butyl ether ⁇ -cyclodextrine Na is suspended in a mixture containing water and ethanol (3:2 V/V). The suspension was heated until a clear solution was obtained. The mixture was concentrated in vacuo. The residue was dried over night at 40°C under vacuum.
  • the XRPD pattern of the isolated inclusion complex does not show any reflections in accordance with crystalline nilotinib hydrochloride.
  • XRPD analysis performed 4 weeks after storing the powder in an alu bag at 55°C/90 RH and 6 months at 40°C/75 RH showed still no reflections in accordance with crystalline nilotinib hydrochloride.
  • Example 2 composition comprising an inclusion complex of amorphous nilotinib hydrochloride : hydro xypropyl-p.cyclodextrin (weight ratio 1:2).
  • HPpCD hydroxypropyl-p.cyclodextrin
  • Kleptose HP® hydroxypropyl-p.cyclodextrin
  • 29 mL of ethanol: 1M HC1 (60:40 v/v) solution under heating (40°C) and magnetic stirring conditions.
  • NLN.hcl Nilotinib hydrochloride monohydrate
  • the resulting dried product was milled in a mortar and sieved through 0.71 mm mesh, obtaining a yellowish, fine powder (1).
  • 1 gram of microcrystalline cellulose and 0.3 gram of croscarmellose sodium were added to the previous powder (1) and were mixed for 10 minutes in a turbula at 72 rpm, obtaining a preliminary blend (2).
  • 0.1 grams of magnesium stearate were sieved though 0.5 mm mesh and mixed with the previous blend (2) for 3 minutes, obtaining the final blend (3). 577 milligrams of the final blend (3) was encapsulated in capsule size 0.
  • XRPD analysis showed that NLN in the final blend as encapsulated was amorphous.
  • Example 3 composition comprising an inclusion complex of amorphous nilotinib hydrochloride : yxyclodextrin (weight ratio 1: 1).
  • ⁇ -cyclodextrin ⁇ -cyclodextrin (yCD, Cavamax W8®) was dissolved in 123 mL of ethanoh lM HC1 (40:60 v/v) solution under heating (40°C) and magnetic stirring conditions. Once the yCD was completely dissolved 2.2 grams of Nilotinib hydrochloride monohydrate (NLN.hcl) were added to the previous solution at the same heating and magnetic stirring conditions. Once NLN.hcl was dissolved, the resulting solution was placed in an oven at 50°C under vacuum.
  • yCD ⁇ -cyclodextrin
  • the resulting dried product was milled in a mortar and sieved through 0.71 mm mesh, obtaining a yellowish, fine powder (1).
  • 0.5 gram of microcrystalline cellulose and 0.2 gram of croscarmellose sodium were added to the previous powder (1) and were mixed for 10 minutes in a turbula at 72 rpm, obtaining a preliminary blend (2).
  • 0.05 grams of magnesium stearate were sieved though 0.5 mm mesh and mixed with the previous blend (2) for 3 minutes, obtaining the final blend (3).
  • 385 milligrams of the final blend (3) were encapsulated in capsule size 1.
  • XRPD analysis showed that NLN in the final blend as encapsulated was amorphous.

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pharmaceutique comprenant un complexe d'inclusion d'ivabradine ou son sel pharmaceutiquement acceptable sous forme amorphe dans une β-cyclodextrine non substituée, et un ou plusieurs excipients pharmaceutiquement acceptables.
PCT/EP2015/080039 2014-12-19 2015-12-16 Composition pharmaceutique comprenant de l'agomélatine amorphe WO2016097011A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP2014078776 2014-12-19
EPPCT/EP2014/078776 2014-12-19

Publications (1)

Publication Number Publication Date
WO2016097011A1 true WO2016097011A1 (fr) 2016-06-23

Family

ID=55025049

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2015/080039 WO2016097011A1 (fr) 2014-12-19 2015-12-16 Composition pharmaceutique comprenant de l'agomélatine amorphe

Country Status (1)

Country Link
WO (1) WO2016097011A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10940149B1 (en) 2018-06-15 2021-03-09 Handa Oncology, Llc Kinase inhibitor salts and compositions thereof
US11389450B2 (en) 2020-01-31 2022-07-19 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US11559485B2 (en) 2020-04-30 2023-01-24 Nanocopoeia, Llc Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib
WO2023208882A1 (fr) * 2022-04-25 2023-11-02 Renata Pharmaceuticals (Ireland) Limited Composition pharmaceutique de nilotinib

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012164578A1 (fr) * 2011-06-02 2012-12-06 Hetero Research Foundation Compositions et procédés de préparation de formulations de nilotinib à libération immédiate
US20140356443A1 (en) * 2012-01-13 2014-12-04 Xspray Microparticles Ab Pharmaceutical composition comprising stable, amorphous, hybrid nanoparticles of at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012164578A1 (fr) * 2011-06-02 2012-12-06 Hetero Research Foundation Compositions et procédés de préparation de formulations de nilotinib à libération immédiate
US20140356443A1 (en) * 2012-01-13 2014-12-04 Xspray Microparticles Ab Pharmaceutical composition comprising stable, amorphous, hybrid nanoparticles of at least one protein kinase inhibitor and at least one polymeric stabilizing and matrix-forming component

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10940149B1 (en) 2018-06-15 2021-03-09 Handa Oncology, Llc Kinase inhibitor salts and compositions thereof
US11052088B2 (en) 2018-06-15 2021-07-06 Handa Oncology, Llc Kinase inhibitor salts, and compositions thereof
US11160805B2 (en) 2018-06-15 2021-11-02 Handa Onocology, Llc Kinase inhibitor salts and compositions thereof
US12064430B2 (en) 2018-06-15 2024-08-20 Handa Oncology, Llc Kinase inhibitor salts and compositions thereof
US12064428B2 (en) 2018-06-15 2024-08-20 Handa Oncology, Llc Kinase inhibitor salts and compositions thereof
US11389450B2 (en) 2020-01-31 2022-07-19 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US11998548B2 (en) 2020-01-31 2024-06-04 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US12016861B2 (en) 2020-01-31 2024-06-25 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US12029740B2 (en) 2020-01-31 2024-07-09 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US12053471B2 (en) 2020-01-31 2024-08-06 Nanocopoeia, Llc Amorphous nilotinib microparticles and uses thereof
US11559485B2 (en) 2020-04-30 2023-01-24 Nanocopoeia, Llc Orally disintegrating tablet comprising amorphous solid dispersion of nilotinib
WO2023208882A1 (fr) * 2022-04-25 2023-11-02 Renata Pharmaceuticals (Ireland) Limited Composition pharmaceutique de nilotinib

Similar Documents

Publication Publication Date Title
ES2672472T3 (es) Composición farmacéutica que comprende ivabradina amorfa
US20170319539A1 (en) Amorphous Empagliflozin
WO2008027600A2 (fr) Compositions d'imatinib
WO2017108605A1 (fr) Composition pharmaceutique comprenant du dasatinib amorphe
WO2016097011A1 (fr) Composition pharmaceutique comprenant de l'agomélatine amorphe
KR20210080225A (ko) 올라파립의 용해도 및 생체이용율이 개선된 조성물
US11517569B2 (en) Vilazodone inclusion complexes, compositions and preparation thereof
US9050326B2 (en) Amido derivatives-contained pharmaceutical composition
KR20190005674A (ko) 주사용 조성물
TWI658841B (zh) 包含苯并咪唑衍生物的新穎調配物
US9248102B2 (en) Tablet containing 5-hydroxy-1H-imidazole-4-carboxamide
US10471156B2 (en) Pharmaceutical composition comprising amorphous lenalidomide
CN113423390A (zh) 阿法比星制剂及其制备方法
EP3079702B1 (fr) Composition pharmaceutique comprenant de l'ivabradine amorphe
JP6210640B2 (ja) ホリナートカルシウム含有錠
AU2013250251B2 (en) Encapsulated formulation
US6984632B1 (en) Complexes of paroxetine, with cyclodextrins or cyclodextrin derivatives
US20170035911A1 (en) Amorphous Cobicistat Solid Dispersion
JP2017002022A (ja) ボリコナゾール含有製剤
EP1988893A2 (fr) Formulation contenant de desloratadine stabilisee au moyen de cyclodextrine
WO2021148992A1 (fr) Compositions pharmaceutiques de raltégravir
WO2007054968A2 (fr) Compositions pharmaceutiques atypiques de mesylate de clopidogrel
JP2020019731A (ja) アムロジピンベシル酸塩の苦味抑制剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15816734

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15816734

Country of ref document: EP

Kind code of ref document: A1