WO2009129297A1 - Compositions pharmaceutiques orales semi-solides - Google Patents

Compositions pharmaceutiques orales semi-solides Download PDF

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Publication number
WO2009129297A1
WO2009129297A1 PCT/US2009/040644 US2009040644W WO2009129297A1 WO 2009129297 A1 WO2009129297 A1 WO 2009129297A1 US 2009040644 W US2009040644 W US 2009040644W WO 2009129297 A1 WO2009129297 A1 WO 2009129297A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
oral pharmaceutical
alcohol
posaconazole
nonionic surfactant
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Application number
PCT/US2009/040644
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English (en)
Inventor
Larry Yun Fang
David Harris
Jiansheng Wan
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Schering Corporation
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Publication of WO2009129297A1 publication Critical patent/WO2009129297A1/fr

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    • 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
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • the present invention relates to novel oral pharmaceutical compositions comprising a semi-solid composition of a weakly basic and poorly-aqueous soluble azole, a monohydric organic alcohol and at least one nonionic surfactant.
  • Such pharmaceutical compositions of posaconazole provide enhanced bioavailability of posaconazole in a solid dosage form as compared to an oral suspension.
  • the invention also relates to methods for treating and/or preventing fiingal infections using said pharmaceutical compositions.
  • weakly basic and poorly-aqueous soluble azole drugs examples include difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, posaconazole, ravuconazole, saperconazole, terconazole, and voriconazole.
  • Certain of these weakly basic and poorly-aqueous soluble azole drugs, including, but not limited to, itraconazole, posaconazole and terconazole have been developed for treatment and/or prevention of fungal infections, including invasive fungal infections.
  • Posaconazole is partially solubilized in an aqueous acidic solvent having a pH of about pH 1 or more acidic.
  • a pH 1 aqueous solvent for example, posaconazole has a solubility of about 790 ⁇ g/mL.
  • posaconazole in contrast, in a solvent less acidic than about pH > 4, posaconazole has a solubility of less than 1 ⁇ g/mL.
  • U.S. Patent No. 5,834,472 ('472 Patent) describes a pharmaceutical composition of posaconazole, a non-ionic surfactant and a diluent.
  • U.S. Patent No. 5,972,381 ('381 Patent) describes pharmaceutical compositions of posaconazole and a soluble or insoluble polymer, such as, povidone or crospovidone, the components being present in particularly recited ratios.
  • U.S. Patent No. 5,846,971 ('971 Patent) describes pharmaceutical capsule compositions of posaconazole coated onto inert beads and a binder. None of the '472, '381, or the '971 Patents describe pharmaceutical compositions comprising posaconazole which provide consistent bioavailability.
  • a solid dosage form of posaconazole which provides low variability in bioavailability and which reduces the "food effect", thus avoiding the need for administration in combination with food.
  • a solid dosage form with sufficient bioavailability would provide a treatment regimen wherein the number of doses administered per day to achieve the desired therapeutic plasma concentration could be reduced.
  • compositions with enhanced bioavailability of a weakly basic and poorly-aqueous soluble azole, including posaconazole would reduce the dose and/or absorption variability required for the same or better therapeutic effect, reduce the cost of goods for the product, and/or reduce the dosing regimen. Solid dosage forms of such drugs would provide greater convenience for patients and hence promote patient compliance.
  • the present invention provides a pharmaceutical composition which can be incorporated into a solid dosage form suitable for oral administration.
  • pharmaceutical compositions of the present invention meet the aforementioned need for reduced variability in the bioavailability of posaconazole, for example, a reduction of variability in bioavailability amongst a population of patients.
  • pharmaceutical compositions of the present invention show a reduction in the food effect associated heretofore with oral administration of pharmaceutical formulations comprising posaconazole.
  • pharmaceutical compositions of the invention are suitable for the preparation of dosage forms having ahigh drug loading, for example, a drug loading of > 100 mg drug per unit dosage form. Such pharmaceutical compositions may provide sufficient bioavailability to eliminate the need for administration with food and/or reduce the number of doses administered per day to achieve the desired therapeutic plasma concentration s) of posaconazole.
  • the present invention provides an oral pharmaceutical composition
  • an oral pharmaceutical composition comprising: a) posaconazole; b) a monohydric organic alcohol; and c) at least one nonionic surfactant; wherein the oral pharmaceutical composition is a semi-solid composition.
  • the present invention provides an oral pharmaceutical composition
  • an oral pharmaceutical composition comprising: a) a weakly basic and poorly-aqueous soluble azole which is difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, ravuconazole, saperconazole, terconazole, or voriconazole; b) a monohydric organic alcohol; and c) at least one nonionic surfactant; wherein the oral pharmaceutical composition is a semi-solid composition.
  • the monohydric organic alcohol is isopropanol, t-butanol, phenol, cresol, or benzyl alcohol, or a mixture of two or more thereof. In some embodiments, the monohydric organic alcohol is benzyl alcohol.
  • At least one nonionic surfactant is a polyoxyethylene fatty alcohol ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene fatty acid ester, a sorbitan ester, glycerol monostearate, a polyethylene glycol, a polypropylene glycol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, an aryl alkyl polyether alcohol, a polyoxyethylene-polyoxypropylene copolymer, a poloxamine, polyvinyl alcohol, polyvinylpyrrolidone, or a macrogol.
  • At least one nonionic surfactant is a polyethylene glycol 660 hydroxystearate, a polyethoxylated castor oil, or a block copolymer of ethylene oxide and propylene oxide.
  • a pharmaceutical composition of the invention in some embodiments optionally it is preferred for a pharmaceutical composition of the invention to be combined with one or more pharmaceutically acceptable excipients.
  • the preparatory method comprises the steps of: (a) dissolving posaconazole in a monohydric organic alcohol; and (b) adding at least one nonionic surfactant while applying vigorous agitation at a temperature from about 35 0 C to about 70 0 C.
  • the present invention provides methods for preparing a a semi-solid composition pharmaceutical composition comprising a weakly basic and poorly-aqueous soluble azole comprising the steps of: (a) dissolving a weakly basic and poorly-aqueous soluble azole in a monohydric organic alcohol; and (b) adding at least one nonionic surfactant while applying vigorous agitation at a temperature from about 35 0 C to about 70 0 C.
  • the azole employed it is preferred for the azole employed to be difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, ravuconazole, saperconazole, terconazole, or voriconazole.
  • Another aspect of the invention provides methods for the treatment and/or prevention of a fungal infection comprising administering a pharmaceutical composition of the present invention, preferably a composition comprising posaconazole, to a patient in need thereof.
  • a pharmaceutical composition of the present invention preferably a composition comprising posaconazole
  • it is preferred to treat patients having a fungal infection is caused by a zygomycetes such as Mucor, Rhizopus, Rhizomucor etc.
  • a dermatophyte such as Tinea corporis, Tinea cruris, Tinea pedis, Tinea barbae, Tinea capitis, Tinea nigra, Tinea favosa, or Tinea Imbricata or any other organism associated with onychomycosis.
  • a pharmaceutical composition of the invention daily in a single or divided dose. In some embodiments administering a pharmaceutical composition of the invention in a daily divided dose, it is preferred to administer the composition of the invention twice-a-day.
  • Figure 1 shows a linear: linear graph of the mean plasma concentration of posaconazole over a time period of 120 hrs post-dose following a single oral administration of 60 mg posaconazole to male cynomolgus monkeys in a semi-solid composition, or, as a comparative example, an oral suspension of posaconazole.
  • Figure 2 is a graph of the mean Cmax concentration of posaconazole following a single oral administration of 60 mg posaconazole to male cynomolgus monkeys in a semisolid composition, or, as a comparative example, an oral suspension of posaconazole.
  • Figure 3 is a graph of the mean exposure (AUC(tf)) of posaconazole following a single oral administration of 60 mg posaconazole to male cynomolgus monkeys in a semisolid composition, or, as a comparative example, an oral suspension of posaconazole.
  • AUC is the area under the plasma concentration-time curve from time zero to a certain time period of the sample.
  • AUC (4h) means the area under the plasma concentration-time curve from time zero to 4 hours.
  • AUC(tf) is the area under the plasma concentration-time curve from time zero to the time of the final quantifiable sample.
  • CL/F is the apparent total clearance of the drug from plasma after oral administration. CL/F is calculated by dividing the dose administered by the AUC.
  • patient refers to an animal including a mammal (e.g., a human).
  • pharmaceutically acceptable excipient refers to a non-toxic excipient that may be administered to a patient, together with the weakly basic and poorly-aqueous soluble azoles as described herein, which does not destroy the pharmacological activity thereof.
  • treating or “treatment” is intended to mean mitigating or alleviating the symptoms of the recited condition, disease or disorder in a mammal such as a human.
  • Pharmacokinetics refers to the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Pharmacokinetic parameters include, but are not limited to "maximum plasma concentration” or “Cmax,” “area under the plasma concentration time curve” or “AUC,” and “time to Cmax” or “Tmax.” As used herein, the term “tl/2" refers to the half-life of the drug.
  • weakly basic and poorly-aqueous soluble azole refers to a compound comprising an azole functional group which is difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, posaconazole, ravuconazole, saperconazole, terconazole, or voriconazole. Especially preferred is posaconazole.
  • the present invention provides oral semi-solid pharmaceutical compositions comprising posaconazole, a monohydric organic alcohol and at least one nonionic surfactant which meet the aforementioned need for sufficient and/or reduced variability in the bioavailability of posaconazole.
  • Such pharmaceutical compositions include, but are not limited to, soft-gel capsules, hard shell gelatin capsules, and liquigel capsules.
  • the pharmaceutical compositions provided herein are suitable for high drug loading dosage forms with > 100 mg drug per unit dosage form.
  • the pharmaceutical compositions of the present invention provide sufficient bioavailability to eliminate the need for administration with food and/or reduce the number of doses administered per day to achieve the desired therapeutic plasma concentration(s) of posaconazole.
  • the ranges (% w/w) of components for the semi-solid compositions provided herein are 5-30 % posaconazole, 5-45 % benzyl alcohol, 20-60% polyethylene glycol 660 hydroxystearate (e.g., Solutol® HS 15), 1-20 % a block copolymer of ethylene oxide and propylene oxide, represented by the formula
  • the present invention also provides oral pharmaceutical compositions comprising a weakly basic and poorly-aqueous soluble azole which is difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, ravuconazole, saperconazole, terconazole, or voriconazole in a semi-solid composition.
  • the weakly basic and poorly-aqueous soluble azole is the antifungal agent fluconazole, itraconazole, ketoconazole, ravuconazole, saperconazole, terconazole, or voriconazole.
  • the weakly basic and poorly-aqueous soluble azole is the antifungal agent itraconazole or terconazole.
  • Posaconazole has the following structure:
  • Posaconazole available from Schering Corporation, Kenilworth, NJ., can be prepared according to Examples 24 and 32 of U.S. Pat. No. 5,661,151 and WO 95/17407. Posaconazole is partially solubilized in a strong acidic aqueous solution with a pH 1 or lower, where it has a solubility of about 790 ⁇ g/mL. In contrast, at pH > 4, posaconazole has a solubility of less than 1 ⁇ g/mL in aqueous solution.
  • Terconazole available from Janssen Pharmaceutica, N.V., Beerse, Belgium and described in U.S. Patent No. 4,223,036, is practically insoluble ( ⁇ 0.1 mg/ml) in water has the following structure:
  • TERCONAZOLE Fluconazole available from Pfizer, New York, N.Y. and described in U.S. Patent No. 6,790,957, is practically insoluble in water (about 1 ug/ml) and has the following structure:
  • Voriconazole (formerly UK 109496), available from Pfizer, New York, N.Y. and described in U.S. Patent No. 5,278,175, has the following structure:
  • Ketoconazole described in U.S. Patent No. 4,144,346, has the following structure:
  • Epirazole (Omeprazole), described in U.S. Patent No. 4,255,431, has the following structure:
  • Difenamizole described in JP 68 6621, which is practically insoluble in water has the following structure:
  • the monohydric alcohol includes, but is not limited to, isopropanol, t-butanol, phenol, cresol, benzyl alcohol or a cycloalkyl alcohol, preferably benzyl alcohol.
  • At least one nonionic surfactant is a polyoxyethylene fatty alcohol ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene fatty acid ester, a sorbitan ester, glycerol monostearate, a polyethylene glycol, a polypropylene glycol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, an aryl alkyl polyether alcohol, a polyoxyethylene-polyoxypropylene copolymer, a poloxamine, polyvinyl alcohol, polyvinylpyrrolidone, or a macrogol.
  • At least one nonionic surfactant is a polyethylene glycol 660 hydroxystearate, a polyethoxylated castor oil, or a block copolymer of ethylene oxide and propylene oxide.
  • the semi-solid compositions of the present invention disclosed herein are formulated into pharmaceutical compositions for oral administration, herein termed "oral" pharmaceutical compositions.
  • Suitable oral dosage forms include, but are not limited to, soft-gel capsules, hard shell gelatin capsules, and liquigel capsules.
  • such oral compositions may optionally further comprise one or more pharmaceutically acceptable excipients.
  • oral dosage forms as described herein have a drug loading capacity of at least 50 mg, 75 mg, 100 mg, or 125 mg per oral dosage form.
  • excipients are well known in the art.
  • excipients include, but are not limited to, surface active agents (e.g., sodium lauryl sulfate and polysorbate 80), drug complexing agents or solubilizers (e.g., polyethylene glycols, caffeine, xanthene, gentisic acid and cylodextrins), diluents (e.g., lactose, mannitol, xylitol, microcrystalline cellulose, calcium diphosphate, and starch), disintegrants (e.g., sodium starch glycolate, sodium alginate, carboxymethyl cellulose sodium, methyl cellulose, low-substituted hydroxypropylcellulose (L-HPC (such as LH-21, and LH-Bl) and croscarmellose sodium), glidants (e.g., silicon dioxide and Talc), binders (e.g., methyl cellulose, microcrystalline cellulose, starch, HP
  • the invention provides methods for preparing the semi-solid pharmaceutical compositions of the present invention.
  • the invention provides methods for preparing a semi-solid composition of posaconazole, comprising: dissolving posaconazole in a monohydric organic alcohol and adding at least one nonionic surfactant while applying vigorous agitation at an elevated temperature.
  • elevated temperatures may be from about 35 0 C to about 70 0 C.
  • Suitable monohydric organic alcohols include isopropanol, t-butanol, phenol, cresol, and benzyl alcohol.
  • the monohydric organic alcohol is benzyl alcohol.
  • At least one nonionic surfactant is a polyoxyethylene fatty alcohol ether, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene fatty acid ester, a sorbitan ester, glycerol monostearate, a polyethylene glycol, a polypropylene glycol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, an aryl alkyl polyether alcohol, a polyoxyethylene- polyoxypropylene copolymer, a poloxamine, polyvinyl alcohol, polyvinylpyrrolidone, or a macrogol.
  • At least one nonionic surfactant is a polyethylene glycol 660 hydroxystearate, a polyethoxylated castor oil, or a block copolymer of ethylene oxide and propylene oxide.
  • Cremophor EL® polyethoxylated castor oil
  • Solutol® HSl 5 polyethylene glycol 660 hydroxystearate
  • the composition is a semi-solid matrix.
  • the resulting mixture is encapsulated in eiterh soft-gel capsules or in hard shell gelatin capsules.
  • Example 1 Two exemplary semi-solid compositions of posaconazole referred to therein as “Exemplary Composition A” and “Exemplary Composition B,” are presented in Table 1.
  • the ranges (% w/w) of components for the semi-solid compositions provided herein are 5-30 % posaconazole, 5- 45 % benzyl alcohol, 20-60% polyethoxylated castor oil (e.g., Cremophor EL®), 1-20 % Poloxamer 188 (e.g., Pluronic® F68).
  • Table 1 Semi-solid compositions of posaconazole.
  • the invention provides methods for preparing a semi-solid composition, comprising: a weakly basic and poorly-aqueous soluble azole which is difenamizole, epirizole, fluconazole, itraconazole, ketoconazole, letrozole, ravuconazole, saperconazole, terconazole, or voriconazole, a monohydric organic alcohol and at least one nonionic surfactant which comprises: dissolving the weakly basic and poorly-aqueous soluble azole in the monohydric organic alcohol followed by addition of a surfactant while applying vigorous agitation at an elevated temperature.
  • Such elevated temperatures may be from about 35 0 C to about 70 0 C.
  • the composition is a semi-solid matrix.
  • the resulting mixture is encapsulated in either soft-gel capsules or in hard shell gelatin capsules.
  • Another aspect of the invention provides methods for the treatment and/or prevention of a fungal infection in a patient comprising administering to the patient a composition according to the invention.
  • the oral pharmaceutical compositions comprise posaconazole.
  • Tinea corporis Tinea cruris, Tinea pedis, Tinea barbae, Tinea capitis, Tinea nigra, Tinea favosa,,or Tinea Imbricat ⁇
  • Trichophyton sp. e.g., but not limited to, Trichophyton rubrum, Trichophyton interdigitale, Trichophyton tonsurans, Trichophyton soudanense, or Trichophyton violaceum
  • Epidermophyton sp. e.g., but not limited to, Epidermophyton floccosum
  • Microsporum sp e.g., but not limited to, Tinea corporis, Tinea cruris, Tinea pedis, Tinea barbae, Tinea capitis, Tinea nigra, Tinea favosa,,or Tinea Imbricat ⁇
  • Trichophyton sp. e.g., but not limited
  • NOXAFILTM posaconazole
  • HSCT hematopoietic stem cell transplant
  • GVHD graft-versus-host disease
  • NOXAFILTM posaconazole
  • oropharmygeal candidiasis including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.
  • the pharmaceutical compositions described herein may be administered to a patient in need thereof every 8 hours, every 12 hours, or every 24 hours.
  • a dose is administered to a patient in need thereof every 12 hours, or every 24 hours.
  • a dose comprises at least one oral dosage form.
  • a dose may comprise at least one additional oral dosage form administered simultaneously with the first dosage form, or within about 5 minutes, or even ten minutes of the first oral dosage form.
  • compositions of the present invention are administered to a patient according to a dosing regimen.
  • a dosing regimen for any particular patient will depend on a variety of factors, including species, age, body weight, body surface area, height, general health, sex, diet, time of administration, rate of excretion, drug combination, specific disease being treated, the severity of the condition, the renal and hepatic function of the patient, the particular active ingredient employed, and the judgment of the treating physician.
  • composition B The two different posaconazole compositions examined were an oral suspension (described in U.S. Publication No. 2003/0055067) as well as a capsule dosage form of the semi-solid composition referred to herein as Exemplary Composition B.
  • Table 3 Mean (CV, %) pharmacokinetic parameters for posaconazole compositions.
  • Table 4 Individual and mean (CV, %) plasma concentration and pharmacokinetic parameters for posaconazole following a single oral administration of 60 mg posaconazole to male cynomolgus monkeys in oral suspension.
  • Table 5 Individual and mean (CV, %) plasma concentration and pharmacokinetic parameters for posaconazole following a single oral administration of 60 mg posaconazole to male cynomolgus monkeys in Capsule (semi-solid posaconazole composition referred to herein as Exemplary Composition B).
  • the semi-solid composition increased posaconazole exposure when compared to the oral suspension indicating an increase in enhanced bioavailability.
  • the difference in mean AUC(tf) and mean Cmax was about 2 times for the semi-solid composition compared to the oral suspension.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

La présente invention concerne des compositions pharmaceutiques semi-solides qui comportent un azole soluble faiblement basique et faiblement aqueux, un alcool organique monohydrique et au moins un tensioactif non ionique. Dans le mode de réalisation idéal, l'azole soluble faiblement basique et faiblement aqueux est du posaconazole. La présente invention concerne également des procédés pour traiter et/ou empêcher des infections fongiques chez un mammifère à l’aide des compositions pharmaceutiques orales décrites ici.
PCT/US2009/040644 2008-04-15 2009-04-15 Compositions pharmaceutiques orales semi-solides WO2009129297A1 (fr)

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US61/045,183 2008-04-15

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013186320A1 (fr) * 2012-06-14 2013-12-19 Sandoz Ag Composition pharmaceutique comprenant du posaconazole cristallin
US9040539B2 (en) 2010-05-19 2015-05-26 Sandoz Ag Process for the preparation of chiral triazolones
US9073904B2 (en) 2010-05-19 2015-07-07 Sandoz Ag Preparation of posaconazole intermediates
US9199919B2 (en) 2010-05-19 2015-12-01 Sandoz Ag Process for the preparation of chiral hydrazides
US9206146B2 (en) 2010-05-19 2015-12-08 Sandoz Ag Purification of posaconazole and of posaconazole intermediates
US9493428B2 (en) 2011-06-16 2016-11-15 Sandoz Ag Process for the preparation of a chiral compound
WO2023148763A1 (fr) * 2022-02-01 2023-08-10 Cipla Limited Compositions pharmaceutiques injectables d'agents antifongiques de type azole

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5834472A (en) * 1996-05-24 1998-11-10 Schering Corporation Antifungal composition with enhanced bioavailability
WO2003017986A1 (fr) * 2001-08-27 2003-03-06 Won Jin Biopharma Co., Ltd. Compositions contenant de l'itraconazole et leurs procedes de preparation
WO2005023262A1 (fr) * 2003-09-09 2005-03-17 Hanmi Pharm. Co., Ltd. Composition orale d'itraconazole non affectee par la nourriture ingere et son procede de preparation
WO2005074890A1 (fr) * 2004-01-30 2005-08-18 Pfizer Italia S.R.L. Formulations pharmaceutiques a matrice semi-solide

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5834472A (en) * 1996-05-24 1998-11-10 Schering Corporation Antifungal composition with enhanced bioavailability
WO2003017986A1 (fr) * 2001-08-27 2003-03-06 Won Jin Biopharma Co., Ltd. Compositions contenant de l'itraconazole et leurs procedes de preparation
WO2005023262A1 (fr) * 2003-09-09 2005-03-17 Hanmi Pharm. Co., Ltd. Composition orale d'itraconazole non affectee par la nourriture ingere et son procede de preparation
WO2005074890A1 (fr) * 2004-01-30 2005-08-18 Pfizer Italia S.R.L. Formulations pharmaceutiques a matrice semi-solide

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9040539B2 (en) 2010-05-19 2015-05-26 Sandoz Ag Process for the preparation of chiral triazolones
US9073904B2 (en) 2010-05-19 2015-07-07 Sandoz Ag Preparation of posaconazole intermediates
US9199919B2 (en) 2010-05-19 2015-12-01 Sandoz Ag Process for the preparation of chiral hydrazides
US9206146B2 (en) 2010-05-19 2015-12-08 Sandoz Ag Purification of posaconazole and of posaconazole intermediates
US9493428B2 (en) 2011-06-16 2016-11-15 Sandoz Ag Process for the preparation of a chiral compound
WO2013186320A1 (fr) * 2012-06-14 2013-12-19 Sandoz Ag Composition pharmaceutique comprenant du posaconazole cristallin
WO2023148763A1 (fr) * 2022-02-01 2023-08-10 Cipla Limited Compositions pharmaceutiques injectables d'agents antifongiques de type azole

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