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WO2002100407A1 - Granules d'itraconazole: formulations pharmaceutiques pour administration orale et procede de preparation de ces dernieres - Google Patents

Granules d'itraconazole: formulations pharmaceutiques pour administration orale et procede de preparation de ces dernieres Download PDF

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Publication number
WO2002100407A1
WO2002100407A1 PCT/CA2002/000894 CA0200894W WO02100407A1 WO 2002100407 A1 WO2002100407 A1 WO 2002100407A1 CA 0200894 W CA0200894 W CA 0200894W WO 02100407 A1 WO02100407 A1 WO 02100407A1
Authority
WO
WIPO (PCT)
Prior art keywords
itraconazole
weight
magnesium
cellulose
sodium
Prior art date
Application number
PCT/CA2002/000894
Other languages
English (en)
Inventor
Horst Zerbe
Richard Swettenham
Original Assignee
Smartrix Technologies Inc.
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 Smartrix Technologies Inc. filed Critical Smartrix Technologies Inc.
Publication of WO2002100407A1 publication Critical patent/WO2002100407A1/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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • ITRACONAZOLE GRANULATIONS PHARMACEUTICAL FORMULATIONS FOR ORAL ADMINISTRATION AND METHOD OF PREPARING SAME
  • the present invention relates to novel formulations as well as to a new granulation method for the antimycotic compound itraconazole.
  • active agents to their respective targets are often limited; in many instances this limitation may be attributed to the chemical nature of the agent.
  • oral delivery is generally ineffective with active agents that are poorly water-soluble.
  • solubility of itraconazole, an anti-fungal drug, in water is less than 1 ⁇ g/ml.
  • Itraconazole is an orally active, broad spectrum anti-fungal agent that is active against mycotic infections. It is structurally related to miconazole and clotrimazole and impairs the synthesis of ergosterol, which is the principal sterol of fungal cell membranes.
  • Water-insoluble or slightly water soluble drugs are only slowly dissolved from a solid formulation.
  • the drug dissolution step is therefore the rate-limiting step in the drug's absorbency which, in turn, has a direct effect on the drug's concentration in the blood stream, and therefore its potency or effectiveness. It is therefore important to increase the dissolution rate of water-insoluble or slightly water soluble drugs in order to improve their solubility and bioavailability.
  • the term "practically insoluble” or "insoluble” is to be understood as it is defined in the United States Pharmacopoeia, i.e. a "very slightly soluble” compound requiring from 1000 to 10,000 parts of water for 1 part of solute.
  • US application 6,100,285 describes the use of microspheres for the delivery of active agents to a target.
  • the formation of the microspheres requires the use of volatile organic acids, such as acetic acid and formic acid.
  • Microsphere formation is reported to occur when the concentration of the acid is decreased, either by dilution with water or by nebulization, leading to the evaporation of the acid. This method results in the release of acidic gases which would require special precautions when carried out on an industrial scale.
  • US application 6,039,981 teaches a method of generating a fused mixture of itraconazole and phosphoric acid.
  • the dissolution of itraconazole from such a mixture in an aqueous solution is said to be greatly enhanced, leading to an increased bioavailability.
  • This method requires the use of large amounts of acid, and additionally, the formation of the fused mixture necessitates high temperatures.
  • PCT International Publication WO 99/33467 discloses an oral preparation for itraconazole having improved bioavailability through the formation of solid dispersions having excellent solubility and increased dissolution rates. These are reported as being prepared by co-dissolving itraconazole and a pH-dependent hydrophilic polymer followed by spray-drying the mixture. The solid dispersions so obtained are then prepared for oral administration.
  • the main drawback of this method is the number of steps involved, making it less advantageous to large-scale operations.
  • PCT International Publication WO 98/57967 discloses an itraconazole of improved solubility. This is obtained by reducing its particle size and by changing its crystallinity from crystalline into amorphous. This procedure requires a careful monitoring of the dissolution-induced drying rate, making it less amenable to large-scale operations.
  • PCT International Publication WO 97/44014 teaches a solid dispersion of itraconazole in a water-soluble polymer which is prepared by subjecting a mixture of itraconazole and a water-soluble polymer to a melt- extrusion process at a temperature ranging from 120 °C to 300 °C. Since there exists a possibility that the water-soluble polymer will decompose if it remains in contact too long with the heating element, the melt-extrusion process has to be carefully monitored.
  • PCT International Publication WO 94/05263 discloses a coated bead preparation wherein a pharmaceutically inert core is coated with a mixture of itraconazole and a pH-independent hydrophilic polymer. The resulting bead is then seal coated. This is a complex process since beads of appropriate dimensions (about 25-30 mesh) have to be carefully prepared in order to minimize their tendency toward agglomeration in the drug coating process. Moreover, the spraying rate and the temperature have to be carefully regulated in order to prevent undesirable drying and moisturization. Furthermore, the application of a seal coating adds an additional 2 steps to the manufacturing process. There remains a need for a novel, orally effective itraconazole formulation having improved in vivo bioavailability.
  • the present invention seeks to meet these and other needs.
  • the present invention relates to a novel, orally effective itraconazole formulation characterized by improved bioavailability, improved solubility and displaying an improved dissolution profile.
  • the present invention relates to a novel method for preparing an orally effective itraconazole formulation exhibiting improved bioavailability, improved solubility and an improved dissolution profile.
  • the present invention also relates to a novel method for preparing an orally effective itraconazole formulation that minimizes manufacturing costs, requires a minimal number of steps and that is amenable to large scale preparations.
  • the present invention includes a novel method for preparing a pharmaceutical dosage, characterized by blending a therapeutically effective amount of itraconazole with selected pharmaceutically acceptable excipients and compressing the blend into tablets.
  • a method for preparing an oral itraconazole formulation comprising the steps of producing a solution by co-dissolving itraconazole and a pH-independent hydrophilic polymer in an appropriate solvent system; forming a powder by combining a first set of excipients in a mixer; forming a granulation by combining the solution containing itraconazole and the pH- independent polymer with the powder composed of the first set of excipients; and finally adding a second set of excipients to the granulation.
  • a fast dissolving oral itraconazole formulation comprising itraconazole and a pH independent hydrophilic polymer and non-active excipients such as a filler and/or binder, a disintegrating agent and a lubricant.
  • Such an embodiment may have the following composition: a) about 20 to 30% by weight of itraconazole; b) about 20 to 30% by weight of hydroxypropyl methylcellulose (HPMC); c) about 20 to 40% by weight of microcrystalline cellulose; d) about 20 to 30% by weight of Lactose Spray Dried; e) about 1.5 to 5% by weight of povidone K29/32; f) about 1.5 to 10% by weight of sodium croscarmellose; g) about 0.1 to 1 % by weight of collo ⁇ dal silicon dioxide; and h) about 0.1 to 1% by weight of magnesium stearate.
  • HPMC hydroxypropyl methylcellulose
  • the fast dissolving itraconazole formulation will have the following composition: a) about 20.0% by weight of itraconazole; b) about 20.0% by weight of hydroxypropyl methylcellulose (HPMC); c) about 30.0% by weight of microcrystalline cellulose; d) about 20.0% by weight of Lactose Spray Dried; e) about 4.0% by weight of povidone K29/32; f) about 7.5% by weight of sodium croscarmellose; g) about 0.5% by weight of collo ⁇ dal silicon dioxide; and h) about 0.5% by weight of magnesium stearate.
  • HPMC hydroxypropyl methylcellulose
  • the present invention provides a novel formulation for the antimycotic compound itraconazole as well as a new granulation process for the preparation of this new formulation.
  • the present invention provides for a method for preparing an oral itraconazole formulation comprising the following steps:
  • step (b) loading a first set of excipients into a fluidized bed spray granulator, forming a powder; and (c) spraying the solution of step (a) onto the powder of step (b), to form a granulation.
  • the present invention also provides for a method for preparing an oral itraconazole formulation comprising the following steps: a) co-dissolving itraconazole and a pH-independent hydrophilic polymer in an appropriate solvent system, producing a solution; b) loading a first set of excipients into a fluidized bed spray granulator, forming a powder; c) spraying the solution of step (a) onto the powder of step (b), to form a granulation; d) mixing said granulation with a polymer solution resulting in the formation of a wet mass and drying said wet mass, forming a second granulation; e) reducing said second granulation, to produce granules; f) adding a second set of excipients to said granules, forming a mixture; and g) blending and compressing the mixture, forming tablets.
  • the present invention additionally provides for a fast- dissolving oral itraconazole formulation comprising an itraconazole and a pH- independent hydrophilic polymer preparation and the following non-active excipients: a filler and/or binder, a disintegrating agent and a lubricant.
  • the generation of the fast dissolving itraconazole formulation involves co-dissolving itraconazole and a pH-independent hydrophilic polymer in a suitable solvent system using a stirrer.
  • the solvent system is preferably selected from either CH 2 CI or a mixture composed of CH 2 CI 2 and EtOH.
  • the solution is then spray dried using a B ⁇ chi Model 190 Mini Spray Dryer.
  • the inlet air temperature is set to a pre-determined target value by adjusting the heat setting, whereas the outlet air temperature is maintained approximately 10 to 15 °C below the former value by adjusting the flow rate of the solution pump, and/or the flow rate of the drying air vacuum.
  • the atomizing air pressure is adjusted as required depending on the viscosity of the solution (itraconazole/polymer/solvent), to produce a suitable spray pattern and droplet size.
  • pH independent hydrophilic polymers such as polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), and polyethylene glycol (PEG), and pH dependent hydrophilic polymers such as aminoalkylmethacrylate copolymer (EUDRAGIT E100TM), have been used in the formation of the fast dissolving formulations of the present invention.
  • PVP polyvinylpyrrolidone
  • HPMC hydroxypropylmethylcellulose
  • PEG polyethylene glycol
  • EUDRAGIT E100TM aminoalkylmethacrylate copolymer
  • a solution comprising itraconazole and HPMC was prepared by dissolving these ingredients in a solvent system composed of methylene chloride and ethanol.
  • Microcrystalline cellulose and Lactose Spray Dried were loaded into a fluidized bed spray granulator and mixed until a homogeneous powder was obtained.
  • the powder was then sprayed with the solution containing itraconazole and HPMC, resulting in the formation of a granulation, onto the carrier.
  • the granulation was then discharged from the fluidized bed spray granulator and loaded into a high speed high sheer mixer, and was mixed with an aqueous solution of polyvinylpyrrolidone (Povidone K29/32).
  • the resulting wet mass was then loaded into a fluidized bed dryer to produce a second granulation.
  • the size of the second granulation was then reduced by passing it through a suitably sized screen, after which additional excipients such as microcrystalline cellulose, sodium croscarmellose, collo ⁇ dal silicon dioxide and magnesium stearate were added.
  • additional excipients such as microcrystalline cellulose, sodium croscarmellose, collo ⁇ dal silicon dioxide and magnesium stearate were added.
  • the resulting powder was blended in a mixer and compressed into tablets.
  • the composition of the present invention comprises a fast dissolving preparation of itraconazole and a suitable pH-independent polymer.
  • pH independent polymers are hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), methylcellulose, guar gum, xanthan gum, gum arabic, tragacantha, and hydroxyethyl cellulose.
  • HPMC hydroxypropyl methylcellulose
  • HPC hydroxypropyl methylcellulose
  • HPC hydroxypropyl cellulose
  • PVP polyvinylpyrrolidone
  • PEG polyethylene glycol
  • methylcellulose methylcellulose
  • guar gum guar gum
  • xanthan gum xanthan gum
  • gum arabic tragacantha
  • hydroxyethyl cellulose hydroxyethyl cellulose
  • HPMC hydroxypropyl methylcellulose
  • the antimycotic composition of the present invention may further comprise non-active excipients such as a filler and/or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent.
  • non-active excipients such as a filler and/or binder, a disintegrating agent, a lubricant, a silica flow conditioner and a stabilizing agent.
  • fillers or binders examples include acacia, alginic acid, carboxymethyl cellulose, dextrin, dibasic calcium phosphate dihydrate, ethyl cellulose, glucose, hydroxyethyl cellulose, hydroxypropyl cellulose, gelatin, guar gum, lactose spray dried DCL 21TM, magnesium aluminum silicate, microcrystalline cellulose PH102TM, polyethylene oxide, polymethacrylates, povidone, sodium alginate and starch.
  • Preferred fillers or binders are microcrystalline cellulose PH102TM, lactose spray dried DCL 21TM, and povidone.
  • disintegrating agents examples include alginic acid, carboxymethylcellulose, hydroxypropyl cellulose (low-substituted), microcrystalline cellulose, powdered cellulose, colloidal silicon dioxide, croscarmellose sodium, crospovidone, magnesium aluminum silicate, methylcellulose, povidone, sodium alginate, disodium disulfite, EDTA, and disodium phosphate.
  • a preferred disintegrating agent is croscarmellose sodium.
  • lubricants examples include calcium stearate, canola oil, glyceryi palmitostearate, lutein, lycopene, magnesium oxide, magnesium aluminum silicate, magnesium carbonate, magnesium oxide, magnesium silicate, magnesium stearate, magnesium trisilicate, maltitol, maltol, maltose, mannitol, mineral oil, poloxamer, polyethylene glycol, polyvinyl alcohol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.
  • a preferred lubricant is magnesium stearate.
  • Example 1 Example of a new itraconazole formulation, as contained in a 500 mg tablet
  • the formulation of the present invention is prepared using the ingredients of Example 1.
  • Itraconazole and hydroxypropyl methylcellulose (HPMC) were co-dissolved in a solvent mixture composed of methylene chloride and ethanol.
  • Microcrystalline cellulose and spray dried lactose were loaded into a fluidized bed spray granulator (Strea-1). The composition was mixed until a homogeneous powder was obtained.
  • the itraconazole / HPMC solution was then sprayed onto the freshly prepared homogeneous powder, resulting in the formation of granules comprising an itraconazole / HPMC preparation, formed on the carrier.
  • Povidone was dissolved in water, and then mixed with the granules.
  • the granules were discharged from the spray dry granulator and loaded into a high speed high sheer mixer, where they were mixed with the aqueous povidone solution.
  • the resulting wet mass was dried in a fluidized bed dryer.
  • the size of the granulation was then reduced by passing it through a suitably-sized screen, generally 30 mesh, after which additional excipients such as microcrystalline cellulose, sodium croscarmellose and collo ⁇ dal silicon dioxide were added.
  • the resulting powder was blended followed by the addition of magnesium stearate and additional blending, using a suitable blender. The powder was then compressed into tablets.
  • the pharmaceutical composition of the present invention may be formulated into various solid pharmaceutical preparations such as tablets, capsules and powders, in accordance with any of the conventional procedures.
  • the present invention is particularly exemplified with a solvent system composed of methylene chloride and ethanol, the present invention is not so limited. Indeed, a solvent system composed of only methylene chloride can also be used. Non-limiting examples of various solvent systems are provided in Table 1. Further, although in the present invention an aqueous solution of povidone is used for mixing with the granules, the present invention is not so limited. Indeed, any aqueous polymer solution or granulating agent suitable for mixing with the granules of the present invention can also be used.

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

Abstract

La présente invention concerne une formulation orale à dissolution rapide comprenant un itraconazole et une préparation polymérique hydrophile indépendante du pH et les excipients non actifs suivants : une charge et/ou un liant, un agent désintégrant et un lubrifiant. L'invention se rapporte également à un procédé de préparation de ces formulations, qui consiste à co-dissoudre de l'itraconazole et un polymère hydrophile indépendant du pH dans un système de solvants approprié, à produire une solution, à charger un premier ensemble d'excipients dans un séchoir atomiseur à lit fluidisé, à former une poudre, et à pulvériser la solution sur la poudre afin de former une granule.
PCT/CA2002/000894 2001-06-12 2002-06-12 Granules d'itraconazole: formulations pharmaceutiques pour administration orale et procede de preparation de ces dernieres WO2002100407A1 (fr)

Applications Claiming Priority (2)

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US29726001P 2001-06-12 2001-06-12
US60/297,260 2001-06-12

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100557680B1 (ko) * 2002-11-23 2006-03-07 한국유나이티드제약 주식회사 이트라코나졸의 용해도 개선을 위한 펠렛제제 및 그제조방법
WO2006066870A1 (fr) * 2004-12-22 2006-06-29 Novartis Ag Compositions pharmaceutiques solides
WO2005107702A3 (fr) * 2004-05-11 2006-10-05 Glenmark Pharmaceuticals Ltd Compositions pharmaceutiques vaginales mucoadhesives a liberation prolongee
US8663684B2 (en) 2008-09-19 2014-03-04 Molkerei Meggle Wasserburg Gmbh & Co. Kg Lactose and cellulose-based tableting aid
CN109172532A (zh) * 2018-10-24 2019-01-11 北京哈三联科技有限责任公司 一种伊曲康唑分散片及其制备方法和应用
WO2022264004A1 (fr) * 2021-06-13 2022-12-22 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de l'itraconazole

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044014A1 (fr) * 1996-05-20 1997-11-27 Janssen Pharmaceutica N.V. Compositions antifongiques avec biodisponibilite amelioree
WO1998042318A1 (fr) * 1997-03-26 1998-10-01 Janssen Pharmaceutica N.V. Comprimes a noyau enrobe d'un agent antifongique et d'un polymere
WO1998057967A1 (fr) * 1997-06-16 1998-12-23 Dong-A Pharmaceutical Co., Ltd. Itraconazole possedant une meilleure solubilite, procede de preparation de ce dernier et composition pharmaceutique pour administration orale comprenant cet itraconazole
WO1999033467A1 (fr) * 1997-12-31 1999-07-08 Choongwae Pharma Corporation Procede et composition d'une preparation orale d'itraconazole

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997044014A1 (fr) * 1996-05-20 1997-11-27 Janssen Pharmaceutica N.V. Compositions antifongiques avec biodisponibilite amelioree
WO1998042318A1 (fr) * 1997-03-26 1998-10-01 Janssen Pharmaceutica N.V. Comprimes a noyau enrobe d'un agent antifongique et d'un polymere
WO1998057967A1 (fr) * 1997-06-16 1998-12-23 Dong-A Pharmaceutical Co., Ltd. Itraconazole possedant une meilleure solubilite, procede de preparation de ce dernier et composition pharmaceutique pour administration orale comprenant cet itraconazole
WO1999033467A1 (fr) * 1997-12-31 1999-07-08 Choongwae Pharma Corporation Procede et composition d'une preparation orale d'itraconazole

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHOWDARY K.P.R. ET AL: "Dissolution rate and formulation studies on solid dispersions of itraconazole.", INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES, (2000) 62/6 (471-474)., XP001105434 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100557680B1 (ko) * 2002-11-23 2006-03-07 한국유나이티드제약 주식회사 이트라코나졸의 용해도 개선을 위한 펠렛제제 및 그제조방법
WO2005107702A3 (fr) * 2004-05-11 2006-10-05 Glenmark Pharmaceuticals Ltd Compositions pharmaceutiques vaginales mucoadhesives a liberation prolongee
WO2006066870A1 (fr) * 2004-12-22 2006-06-29 Novartis Ag Compositions pharmaceutiques solides
JP2008524291A (ja) * 2004-12-22 2008-07-10 ノバルティス アクチエンゲゼルシャフト 固体医薬組成物
US8663684B2 (en) 2008-09-19 2014-03-04 Molkerei Meggle Wasserburg Gmbh & Co. Kg Lactose and cellulose-based tableting aid
CN109172532A (zh) * 2018-10-24 2019-01-11 北京哈三联科技有限责任公司 一种伊曲康唑分散片及其制备方法和应用
WO2022264004A1 (fr) * 2021-06-13 2022-12-22 Glenmark Pharmaceutical Limited Composition pharmaceutique comprenant de l'itraconazole

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