WO2017032908A1 - Composition pharmaceutique comprenant du posaconazole amorphe - Google Patents

Composition pharmaceutique comprenant du posaconazole amorphe Download PDF

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Publication number
WO2017032908A1
WO2017032908A1 PCT/EP2016/078902 EP2016078902W WO2017032908A1 WO 2017032908 A1 WO2017032908 A1 WO 2017032908A1 EP 2016078902 W EP2016078902 W EP 2016078902W WO 2017032908 A1 WO2017032908 A1 WO 2017032908A1
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Prior art keywords
composition according
posaconazole
methacrylic acid
weight ratio
methyl methacrylate
Prior art date
Application number
PCT/EP2016/078902
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English (en)
Inventor
Manuel GAGO GUILLAN
Luis Nogueiras Nieto
Lisardo Alvarez Fernandez
Jose VELADA CALZADA
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Synthon B.V.
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Publication date
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Publication of WO2017032908A1 publication Critical patent/WO2017032908A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin

Definitions

  • Posaconazole chemically 4-(4-(4-(4-(((3R,5R)-5-(2,4-difluorophenyl)-5-(l,2,4-triazol- l-ylmethyl)oxolan-3-yl)methoxy)phenyl)piperazin-l-yl)phenyl)-2-((2 l S , ,35')-2-hydroxypentan- 3-yl)-l,2,4-triazol-3-one of formula (I),
  • Noxafil ® is a broad-spectrum antifungal agent of the triazole class for the treatment of invasive fungal infections.
  • the compound has been first disclosed in W09517407.
  • Posaconazole is marketed by Merck Sharp & Dohme under the brand name Noxafil ® .
  • Noxafil ® is supplied both for oral and intravenous administration, as oral suspension, as delayed-release gastroresistant tablet and as concentrate for solution for infusion.
  • the delayed-release tablet is available in the strength of 100 mg.
  • the marketed formulation has been disclosed in WO2009129300.
  • posaconazole Three polymorphic forms of posaconazole, viz. form I, II and III, have been described in WO9918097. Other polymorphic forms of posaconazole are disclosed in WO2009147075, WO20100000668, WO2011003992 and WO2015092595.
  • Posaconazole is poorly soluble in water. In the stomach, posaconazole has a solubility of approximately 0.8 mg/ml. At pH 6.4 or higher, the solubility of posaconazole is less than 1 ⁇ g/ml. The solubility of amorphous forms is higher compared to the solubility of crystalline forms, thus it would be desirable to have posaconazole available in amorphous form.
  • Amorphous posaconazole and processes of its preparation are disclosed in WO2011158248, WO2013042138, CN104370894, WO2015059716 and WO2015092595.
  • amorphous posaconazole as such is not stable and therefore not suitable for use on
  • WO2009129300 discloses pharmaceutical compositions comprising posaconazole dissolved or molecularly dispersed in a hydroxypropylmethylcellulose-derivative polymer.
  • the composition is prepared by the process of hot melt extrusion.
  • the main advantage of the hot melt extrusion process is that it is a continuous manufacturing process.
  • the drawback of this technique is the high temperatures it requires, therewith increasing the risk of
  • WO2015154718 discloses pharmaceutical compositions comprising solid dispersions of posaconazole and vinyl pyrrolidone-vinyl acetate copolymer or a polymer containing ethylene glycol units.
  • the carrier material may in addition comprise an enteric polymer.
  • the solid dispersions are prepared by the process of hot melt extrusion.
  • US20150231081 discloses a delayed release composition
  • a delayed release composition comprising posaconazole dissolved or molecularly dispersed in a polymer other than a hydroxypropylmethylcellulose derived polymer, wherein the composition is prepared by hot melt extrusion.
  • CN 104510707 and CN 10472187 disclose solid dispersions comprising posaconazole and a water soluble polymer (e.g. an amphiphilic copolymer) or hydroxypropylmethylcellulose respectively.
  • the solid dispersions are prepared by hot melt extrusion, freeze drying or spray drying. The techniques of freeze drying and spray drying require specific, expensive equipment and often result in rather fluffy, low density material, which is difficult to process further into the final drug product.
  • CN104721141 discloses solid dispersions comprising posaconazole and a polymer skeleton comprising of two polymers.
  • the first polymer realizes a uniform dispersion of posaconazole in the polymer skeleton and the second polymer constructs a microenvironment for improving the dissolution rate of posaconazole in aqueous environment.
  • the polymer skeleton comprises Soluplus ® and Eudragit ® E100.
  • the solid dispersion is prepared by the process of hot melt extrusion or spray drying.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a solid dispersion of posaconazole and at least two different enteric polymers, wherein the solid dispersion is obtained by applying the process of wet granulation.
  • Said pharmaceutical composition may be used in the treatment of invasive fungal infections.
  • Posaconazole is poorly soluble in water. In the stomach, posaconazole has a solubility of approximately 0.8 mg/ml. At pH 6.4 or higher, the solubility of posaconazole is less than 1 ⁇ g/ml.
  • solid dispersion has been defined as a dispersion of one or more Active Pharmaceutical Ingredients (APIs) in an inert carrier or matrix at the solid state, prepared by a solvent or melting process or a combination of the two.
  • APIs Active Pharmaceutical Ingredients
  • the solid dispersions are divided into crystalline solid dispersions and amorphous solid dispersions respectively.
  • Amorphous carriers used are mostly polymers.
  • the API is dispersed in very small size and exists in supersaturated state in amorphous carriers because of forced solubilization.
  • the amorphous carriers can increase the wettability and dispersibility of drugs as well as inhibit the precipitation process of drugs when amorphous solid dispersions are dissolved in water. These properties along with the fast dissolution rate of amorphous carriers enhance the drug solubility and release rate.
  • the number of marketed products arising from solid dispersion approaches is very low. This low number is mainly due to scale-up problems and physicochemical instability in the manufacturing process or during storage leading to phase separation and crystallization (Vo et. al, Eur. J. Pharm. Biopharm., 85 (2013) 799-813).
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a solid dispersion of posaconazole and at least two different enteric polymers, wherein the solid dispersion is obtained by applying the process of wet granulation.
  • This conventional technique can be carried out with equipment commonly used in pharmaceutical industry.
  • a pharmaceutical composition obtained by applying the process of wet granulation, comprising a solid dispersion of posaconazole and at least two different enteric polymers, i.e. polymers that prevent dissolution or disintegration in the gastric environment, mimics the dissolution of the Noxafil ® gastroresistant tablet.
  • the weight ratio of posaconazole to the total amount of enteric polymers ranges from 1: 1.5 to 1:5. More preferably, the weight ratio of posaconazole to the total amount of enteric polymers ranges from 1:2 to 1:4.
  • one of the enteric polymers used in accordance with the present invention is an anionic copolymer based on methacrylic acid and methyl metha- crylate.
  • the weight ratio of methacryclic acid to methyl methacrylate in the copolymer is 1 : 1.
  • a typical example of a commercially available polymer includes Eudragit ® L100.
  • a second enteric polymer used in accordance with the present invention is hydroxypropylcellulose acetate succinate (HPMCAS), also known as hypromellose acetate succinate. It is a mixture of acetic acid and monosuccinic acid esters of hydroxypropylmethyl cellulose.
  • HPMCAS is available in three grades, differentiated by the degree of substitution, resulting in a pH dependent dissolution (low, L; medium M; high H). Each grade is available in two particle sizes (cohesive fine powder, F; free-flowing granules, G). In principle, every grade of HPMCAS may be used in accordance with the present invention. Grade M is a particularly preferred grade.
  • the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and HPMCAS. Even more preferably, the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and HPMCAS, wherein the weight ratio of methacryclic acid to methyl methacrylate in the copolymer is 1: 1.
  • the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and HPMCAS, wherein the weight ratio of posaconazole to the anionic copolymer to HPMCAS ranges from 1:0.9:0.9 to 1: 1:3. A particularly preferred range is from 1: 1: 1 to 1: 1:2.
  • a second enteric polymer used in accordance with the present invention is an anionic copolymer based on methacrylic acid and ethyl acrylate.
  • the weight ratio of methacryclic acid to ethyl acrylate in the copolymer is 1: 1.
  • a typical example of a commercially available polymer includes Eudragit ® L 100-55.
  • the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and an anionic copolymer based on methacrylic acid and ethyl acrylate.
  • the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and methacrylic acid and ethyl acrylate, wherein the weight ratio of methacryclic acid to methyl methacrylate and methacrylic acid to ethyl acrylate in the copolymers is 1: 1.
  • the pharmaceutical composition of the present invention comprises a solid dispersion of posaconazole, an anionic copolymer based on methacrylic acid and methyl methacrylate and an anionic copolymer based on methacrylic acid and ethyl acrylate, wherein the weight ratio of posaconazole to the anionic copolymer based on methacrylic acid and methyl methacrylate to the anionic copolymer based on methacrylic acid and ethyl acrylate ranges from 1:0.8:0.7 to 1:2:2.
  • the pharmaceutical composition of the present invention comprising a solid dispersion of posaconazole and at least two enteric polymers, further comprises one or more pharma- ceutically 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 pharmaceutical composition is in the form of a tablet. It may optionally be coated with a film coat comprising, in essence, any suitable inert coating material known in the art.
  • the pharmaceutical composition of the present invention is obtained by applying the process of wet granulation.
  • posaconazole and the enteric polymers are dissolved in a solvent mixture.
  • the process of wet granulation in accordance with the present invention is carried out in the non-toxic solvent mixture comprising water and acetone.
  • the weight ratio of acetone to water ranges from 65:35 to 95:5. At these ratios, optimal solubility is achieved.
  • the solubility of posaconazole may be further increased by heating the solvent mixture.
  • the resulting solution is added to a diluent.
  • the addition of the solution to the diluent is performed by spraying the solution over the diluent in a fluid bed reactor.
  • 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 solvent is evaporated.
  • the evaporation is carried out by techniques known to a person of ordinary skill in the art.
  • part of the obtained granules is compressed in order to increase the density of the final drug product, before mixing the granules with further excipients.
  • pharmaceutically acceptable excipients are chosen from one or more diluents, binders, disintegrants or lubricants. Most preferably, the further excipients are chosen from one or more diluents, one or more disintegrants and one or more lubricants.
  • 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 croscarmel- lose sodium, crospovidone or sodium starch glycolate. 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.
  • the pharmaceutical composition of the present invention exhibits excellent long term stability. Even after 3 months at 40°C/75% RH, no conversion into any crystalline form of posaconazole was observed. Moreover, the pharmaceutical composition of the present invention is very suitable for production on commercial scale.
  • the pharmaceutical composition of the invention displays delayed release of posaconazole.
  • the dissolution rate of the composition is less than 8% in 2 hours when tested in aqueous hydrochloric acid pH 2.0 and at least 75% in 10 minutes when tested in a phosphate buffer with 0.5% SDS pH 6.8 in a USP apparatus II at 75 rpm, 37°C.
  • the solid dispersion of posaconazole and at least two different enteric polymers remains in amorphous form.
  • 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, Triplex/ Alu and Alu/Alu. A particularly preferred blister pack material is Alu/Alu.
  • 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 invasive fungal infections.
  • the following examples are intended to illustrate the scope of the present invention but not to limit it thereto.
  • Example 1 Pharmaceutical composition comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1:1) and HPMCAS (1:3:1)
  • the tablets comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1: 1) and HPMCAS (1:3: 1) have the composition as given in table 1.
  • Posaconazole was dissolved in a mixture of acetone:water 9: 1. HPMCAS was added slowly. The mixture was stirred until a solution was obtained. Methacrylic acid - methyl methacrylate copolymer (1: 1) (Eudragit ® L100) was added. The mixture was stirred until a solution was obtained. The obtained solution was sprayed over microcrystalline cellulose in a fluid bed dryer. The obtained granules were dried and sieved through an appropriate mesh size sieve. 60% of the total amount of sieved granules was compressed under monitored humidity conditions on a rotary tabletting machine using flat punches. The tablets thus obtained were milled through appropriate mesh size sieves.
  • Microcrystalline cellulose and sodium croscarmellose were sieved through an appropriate sieve and mixed with the obtained compacted granules and the remaining 40% of the sieved non-compacted granules in a suitable blender.
  • Magnesium stearate was sieved through an appropriate sieve and mixed with the blend in a suitable blender.
  • the homogeneous blend obtained, was compressed using a rotating tablet press using appropriate punches.
  • the tablets were coated with an Opadry II suspension. Tablet weight increase was 3%.
  • the tablets were packed in alu-alu blisters.
  • the tablets were stored at long term (25°C/60% RH) and accelerated (40°C/75% RH) conditions. The tablets show excellent stability after storage for 3 months.
  • Example 2 Pharmaceutical composition comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1:1) and HPMCAS (1:1:1)
  • the tablets comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1: 1) and HPMCAS (1: 1: 1) have the composition as given in table 2.
  • Posaconazole was dissolved in a mixture of acetone:water 9: 1 at 35-40°C. HPMCAS was added slowly. The mixture was stirred until a solution was obtained. Methacrylic acid - methyl methacrylate copolymer (1: 1) (Eudragit ® LI 00) was added. The mixture was stirred until a solution was obtained. The obtained solution was sprayed over microcrystalline cellulose in a fluid bed dryer. The obtained granules were dried and sieved through an appropriate mesh size sieve. Microcrystalline cellulose and sodium croscarmellose were sieved through an appropriate sieve and mixed with the granules in a suitable blender.
  • Magnesium stearate was sieved through an appropriate sieve and mixed with the blend in a suitable blender.
  • the tablets were coated with an Opadry II suspension. Tablet weight increase was 3%.
  • the tablets were packed in alu-alu blisters.
  • the tablets were stored at long term (25°C/60 RH) and accelerated (40°C/75 RH) conditions. The tablets show excellent stability after storage for 3 months. XRPD analysis performed, showed no reflections in accordance with crystalline posaconazole.
  • Example 3 Pharmaceutical composition comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1:1) and a copolymer of methacrylic acid and ethyl acrylate (1:1) (1:1:0.8)
  • the tablets comprising a solid dispersion of posaconazole, a copolymer of methacrylic acid and methyl methacrylate (1: 1) and a copolymer of methacrylic acid and ethyl acrylate (1: 1) (1: 1:0.8) have the composition as given in table 3.
  • Table 3 Table 3
  • Posaconazole was dissolved in a mixture of acetone:water 9: 1 at about 45°C.
  • Methacrylic acid - methyl methacrylate copolymer (1: 1) (Eudragit ® L100) and methacrylic acid - ethyl acrylate copolymer (1: 1) (Eudragit ® L100-55) were added. The mixture was stirred at 45°C until a solution was obtained. The obtained solution was sprayed over microcrystalline cellulose in a fluid bed dryer. The obtained granules were dried and sieved through an appropriate mesh size sieve. Microcrystalline cellulose and sodium croscarmellose were sieved through an appropriate sieve and mixed with the granules in a suitable blender. Magnesium stearate was sieved through an appropriate sieve and mixed with the blend in a suitable blender.
  • the homogeneous blend obtained was compressed using a rotating tablet press using appropriate punches.
  • the tablets were coated with an Opadry II suspension. Tablet weight increase was 3%.
  • the tablets were packed in alu-alu blisters.
  • the tablets were stored at long term (25°C/60 RH) and accelerated (40°C/75 RH) conditions.
  • the tablets show excellent stability after storage for 3 months.
  • XRPD analysis performed, showed no reflections in accordance with crystalline posaconazole.

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Abstract

La présente invention concerne une composition pharmaceutique comprenant une dispersion une dispersion de posaconazole et au moins deux polymères entériques différents, ladite dispersion solide étant obtenue par application du processus de granulation par voie humide. L'invention concerne en outre l'utilisation de ladite composition en tant que médicament, notamment dans le traitement d'infections fongiques invasives.
PCT/EP2016/078902 2016-07-08 2016-11-25 Composition pharmaceutique comprenant du posaconazole amorphe WO2017032908A1 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342399A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Compositions pharmaceutiques comprenant du posaconazole et procédé de fabrication
US10702520B1 (en) 2019-01-29 2020-07-07 Slayback Pharma Llc Pharmaceutical compositions of posaconazole
WO2022034232A1 (fr) 2020-08-13 2022-02-17 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Formulation à haute résistance entérosoluble contenant du posaconazole
EP4091604A1 (fr) 2021-11-25 2022-11-23 Alfred E. Tiefenbacher (GmbH & Co. KG) Granules contenant du posaconazole
WO2023012378A1 (fr) 2021-11-25 2023-02-09 Alfred E. Tiefenbacher (Gmbh Und Co. Kg) Granules contenant du posaconazole
US11708463B2 (en) 2018-04-06 2023-07-25 Capsugel Belgium Nv Spray drying process for low aspect ratio particles comprising poly[(methyl methacrylate)-co-(methacrylic acid)]

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995017407A1 (fr) 1993-12-21 1995-06-29 Schering Corporation Tetrahydrofuranes antifongiques
WO1999018097A1 (fr) 1997-10-07 1999-04-15 Schering Corporation Olymorphe antifongique cristallin
WO2009129300A2 (fr) 2008-04-15 2009-10-22 Schering Corporation Compositions à haute densité contenant du posaconazole et formulations comprenant de telles compositions
WO2009129301A2 (fr) * 2008-04-15 2009-10-22 Schering Corporation Compositions pharmaceutiques orales dans une dispersion solide moléculaire
WO2009147075A2 (fr) 2008-06-02 2009-12-10 Sandoz Ag Compositions pharmaceutiques contenant une forme cristalline de posaconazole
WO2010000668A1 (fr) 2008-07-03 2010-01-07 Sandoz Ag Forme cristalline de posaconazole
WO2011003992A1 (fr) 2009-07-09 2011-01-13 Sandoz Ag Forme cristalline du posaconazole
WO2011158248A2 (fr) 2010-05-12 2011-12-22 Glenmark Generics Limited Procédé pour la préparation de posaconazole et forme polymorphique cristalline v de posaconazole
WO2013042138A2 (fr) 2011-09-19 2013-03-28 Msn Laboratories Limited Procédé pour la préparation de médicament antifongique triazole, ses intermédiaires et polymorphes de celui-ci
EP2837391A1 (fr) * 2013-08-12 2015-02-18 Shin-Etsu Chemical Co., Ltd. Succinate d'acétate d'hypromellose en tant que support d'extrusion à chaud, composition d'extrusion à chaud et procédé de production d'un extrudat thermofusible
CN104370894A (zh) 2014-10-21 2015-02-25 江苏恒盛药业有限公司 无定型泊沙康唑的制备工艺
CN104510707A (zh) 2013-09-26 2015-04-15 博瑞生物医药技术(苏州)有限公司 一种泊沙康唑固体分散体及其制备方法
WO2015059716A2 (fr) 2013-10-22 2015-04-30 Msn Laboratories Private Limited Procédé amélioré pour préparer du ((3s,5r)-5-((1h-1,2,4-triazol-1-yl)méthyl)-5-(2,4-difluorophényl)tétrahydrofuran-3-yl)méthyl-4-méthylbenzènesulfonate
CN104721827A (zh) 2013-12-18 2015-06-24 博瑞生物医药技术(苏州)有限公司 一种难溶性抗真菌药物固体分散体及其制备方法
CN104721141A (zh) 2013-12-18 2015-06-24 博瑞生物医药技术(苏州)有限公司 抗真菌药物固体分散体
WO2015092595A1 (fr) 2013-12-18 2015-06-25 Avanthera S.A. Forme cristalline de posaconazole
US20150231081A1 (en) 2014-02-20 2015-08-20 Cadila Healthcare Limited Delayed release posaconazole tablets
WO2015154718A1 (fr) 2014-04-11 2015-10-15 上海宣泰医药科技有限公司 Composition pharmaceutique à base de posaconazole, ainsi que procédé de préparation, utilisation et préparation pharmaceutique de celle-ci

Patent Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995017407A1 (fr) 1993-12-21 1995-06-29 Schering Corporation Tetrahydrofuranes antifongiques
WO1999018097A1 (fr) 1997-10-07 1999-04-15 Schering Corporation Olymorphe antifongique cristallin
WO2009129300A2 (fr) 2008-04-15 2009-10-22 Schering Corporation Compositions à haute densité contenant du posaconazole et formulations comprenant de telles compositions
WO2009129301A2 (fr) * 2008-04-15 2009-10-22 Schering Corporation Compositions pharmaceutiques orales dans une dispersion solide moléculaire
WO2009147075A2 (fr) 2008-06-02 2009-12-10 Sandoz Ag Compositions pharmaceutiques contenant une forme cristalline de posaconazole
WO2010000668A1 (fr) 2008-07-03 2010-01-07 Sandoz Ag Forme cristalline de posaconazole
WO2011003992A1 (fr) 2009-07-09 2011-01-13 Sandoz Ag Forme cristalline du posaconazole
WO2011158248A2 (fr) 2010-05-12 2011-12-22 Glenmark Generics Limited Procédé pour la préparation de posaconazole et forme polymorphique cristalline v de posaconazole
WO2013042138A2 (fr) 2011-09-19 2013-03-28 Msn Laboratories Limited Procédé pour la préparation de médicament antifongique triazole, ses intermédiaires et polymorphes de celui-ci
EP2837391A1 (fr) * 2013-08-12 2015-02-18 Shin-Etsu Chemical Co., Ltd. Succinate d'acétate d'hypromellose en tant que support d'extrusion à chaud, composition d'extrusion à chaud et procédé de production d'un extrudat thermofusible
CN104510707A (zh) 2013-09-26 2015-04-15 博瑞生物医药技术(苏州)有限公司 一种泊沙康唑固体分散体及其制备方法
WO2015059716A2 (fr) 2013-10-22 2015-04-30 Msn Laboratories Private Limited Procédé amélioré pour préparer du ((3s,5r)-5-((1h-1,2,4-triazol-1-yl)méthyl)-5-(2,4-difluorophényl)tétrahydrofuran-3-yl)méthyl-4-méthylbenzènesulfonate
CN104721827A (zh) 2013-12-18 2015-06-24 博瑞生物医药技术(苏州)有限公司 一种难溶性抗真菌药物固体分散体及其制备方法
CN104721141A (zh) 2013-12-18 2015-06-24 博瑞生物医药技术(苏州)有限公司 抗真菌药物固体分散体
WO2015092595A1 (fr) 2013-12-18 2015-06-25 Avanthera S.A. Forme cristalline de posaconazole
US20150231081A1 (en) 2014-02-20 2015-08-20 Cadila Healthcare Limited Delayed release posaconazole tablets
WO2015154718A1 (fr) 2014-04-11 2015-10-15 上海宣泰医药科技有限公司 Composition pharmaceutique à base de posaconazole, ainsi que procédé de préparation, utilisation et préparation pharmaceutique de celle-ci
CN104370894A (zh) 2014-10-21 2015-02-25 江苏恒盛药业有限公司 无定型泊沙康唑的制备工艺

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
VO, EUR. J. PHARM. BIOPHARM., vol. 85, 2013, pages 799 - 813

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3342399A1 (fr) * 2016-12-31 2018-07-04 Abdi Ibrahim Ilac Sanayi ve Ticaret A.S. Compositions pharmaceutiques comprenant du posaconazole et procédé de fabrication
US11708463B2 (en) 2018-04-06 2023-07-25 Capsugel Belgium Nv Spray drying process for low aspect ratio particles comprising poly[(methyl methacrylate)-co-(methacrylic acid)]
US10702520B1 (en) 2019-01-29 2020-07-07 Slayback Pharma Llc Pharmaceutical compositions of posaconazole
WO2022034232A1 (fr) 2020-08-13 2022-02-17 Alfred E. Tiefenbacher (Gmbh & Co. Kg) Formulation à haute résistance entérosoluble contenant du posaconazole
EP4091604A1 (fr) 2021-11-25 2022-11-23 Alfred E. Tiefenbacher (GmbH & Co. KG) Granules contenant du posaconazole
WO2023012378A1 (fr) 2021-11-25 2023-02-09 Alfred E. Tiefenbacher (Gmbh Und Co. Kg) Granules contenant du posaconazole

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