WO2015114314A1 - Pharmaceutical composition comprising abiraterone - Google Patents

Pharmaceutical composition comprising abiraterone Download PDF

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Publication number
WO2015114314A1
WO2015114314A1 PCT/GB2015/050175 GB2015050175W WO2015114314A1 WO 2015114314 A1 WO2015114314 A1 WO 2015114314A1 GB 2015050175 W GB2015050175 W GB 2015050175W WO 2015114314 A1 WO2015114314 A1 WO 2015114314A1
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WIPO (PCT)
Prior art keywords
pharmaceutical composition
abiraterone
composition according
tablet
pharmaceutically acceptable
Prior art date
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PCT/GB2015/050175
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English (en)
French (fr)
Inventor
Geena Malhotra
Preeti Raut
Original Assignee
Cipla Limited
King, Lawrence
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Publication of WO2015114314A1 publication Critical patent/WO2015114314A1/en

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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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a pharmaceutical composition comprising a 17"-hydroxylase/C 17,20-lyase enzyme (CYP17) inhibitor, to a process for preparing such pharmaceutical composition and to the use of the said pharmaceutical composition for the treatment of prostate cancer.
  • CYP17 17"-hydroxylase/C 17,20-lyase enzyme
  • Prostate cancer is one of the most commonly diagnosed solid organ malignancies in the United States (US) and remains the second leading cause of cancer deaths among American males. Approximately 240,000 new diagnoses of prostate cancer and over 28,000 deaths were estimated in the US in 2012. Prostate cancer deaths are typically the result of metastatic castration- resistant prostate cancer (mCRPC), and historically the median survival for males with mCRPC has been less than two years.
  • US United States
  • mCRPC metastatic castration- resistant prostate cancer
  • Abiraterone acetate is an irreversible inhibitor of CYP 17, an androgen biosynthesis inhibitor. This enzyme is expressed in testicular, adrenal and prostatic tumor tissues. Inhibition of this enzyme results in further reduction of testosterone synthesis in patients already undergoing androgen deprivation therapy.
  • Abiraterone acetate in combination with prednisone is indicated for the treatment of patients with mCRPC who have received prior chemotherapy of docetaxel.
  • Abiraterone is structurally represented as:
  • WO2013012959 discloses a composition comprising a solid dispersion of abiraterone and a solid matrix, wherein abiraterone is dispersed in the solid matrix.
  • US2013251804 discloses a dosage form of abiraterone in the form of a rounded pill with a water- soluble polymer coating having a thickness between 10 and 500 micrometers.
  • WO2013164473 discloses abiraterone acetate dissolved or dispersed in a carrier, wherein the carrier comprises one or more lipid excipients.
  • WO2014145813 discloses a method of producing a composition comprising nanoparticles of abiraterone acetate. The method comprises dry milling a composition comprising abiraterone acetate, a millable grinding compound, a facilitating agent and one or both of an antioxidant and a sequestering agent, in a mill comprising a plurality of milling bodies, for a time period sufficient to produce a composition comprising fine particles of the abiraterone acetate.
  • WO2014009436 discloses a nanosuspension comprising particles of abiraterone acetate or a pharmaceutically acceptable salt, hydrate or solvate thereof having an average particle size, d(0.5), of less than 1000 nm.
  • the recommended dose of abiraterone acetate is 1000 mg per day (QD), in combination with prednisone 5 mg twice a day (bid). Tablets comprising 250 mg abiraterone acetate are sold under the trade name Zytiga ® . Thus, the required dosage is comprised in four Zytiga ® tablets that have to be administered orally once a day.
  • abiraterone has pharmacokinetic properties that are affected by the prandial status of a patient receiving the treatment, i.e. it exhibits a "food effect".
  • bioavailability of abiraterone increases with food, more specifically 10 times in a fed state as compared to a fasted state.
  • maximum or peak serum concentration (Cmax) and area under the curve (AUC) are elevated 5 to 7 times when compared with the fasted state, whereas the C max and AUC are elevated 10 to 17 times after a high fat meal. This leads to erratic and unpredictable bioavailability.
  • abiraterone is recommended to be administered in a fasted state in an attempt to minimize the food effect.
  • Patients receive specific instructions to administer Zytiga ® on an empty stomach, that is, no food intake during a period of 2 hours before dosing, and for a period one hour after dosing.
  • Zytiga ® is administered in a fasted state in an attempt to minimize the food effect.
  • Zytiga ® has poor bioavailability in fasted subjects and must therefore be administered at a very high daily dose of 1000 mg.
  • Administration of an abiraterone composition with food may change its bioavailability by affecting either the drug substance or the composition in which the drug substance is formulated.
  • abiraterone may be hampered by factors such as emesis and ingestion and would ultimately lead to decreased bioavailability of abiraterone.
  • the resulting composition of abiraterone should be stable as well as exhibit optimal dissolution properties.
  • the dry milling process disclosed in WO2014145813 may generally lead to particle agglomeration of small primary particles to larger secondary particles which could be a major hindrance in the milling process.
  • the object of the present invention is to provide a pharmaceutical composition
  • a pharmaceutical composition comprising abiraterone optionally with one or more pharmaceutically acceptable excipients.
  • Another object of the present invention is to provide a rapid release pharmaceutical composition comprising abiraterone.
  • Another object of the present invention is to provide a pharmaceutical composition comprising abiraterone which ensure patient compliance.
  • Another object of the present invention is to provide a pharmaceutical composition comprising abiraterone devoid of any food effect.
  • Another object of the present invention is to provide a pharmaceutical composition comprising abiraterone for once a day administration.
  • Another object of the present invention is to provide a process for preparing a pharmaceutical composition comprising abiraterone optionally with one or more pharmaceutically acceptable excipients.
  • Another object of the present invention is to provide a method of treating prostate cancer by administering a pharmaceutical composition comprising abiraterone.
  • Another object of the present invention is to provide the use of pharmaceutical composition comprising abiraterone for the treatment of prostate cancer.
  • a pharmaceutical composition comprising abiraterone and one or more pharmaceutically acceptable excipients.
  • a process for preparing a pharmaceutical composition comprising admixing one or more pharmaceutically acceptable excipients with abiraterone.
  • a pharmaceutical composition comprising abiraterone for use in the treatment of prostate cancer.
  • a method of treatment of prostate cancer which comprises administering a pharmaceutical composition comprising abiraterone.
  • Abiraterone is commercially available as a conventional tablet formulation for the treatment of prostate cancer.
  • the required dosage is comprised in four abiraterone tablets that have to be administered orally once a day.
  • cancer patients are usually on a multiple drug regimen demanding the administration of large numbers of tablets or capsules often along with intravenous therapy.
  • Patient compliance in such a regimen can be addressed by decreasing the number of tablets or capsules administered as well as the type of dosage forms that are administered, with due consideration to the bioavailability of the administered drug. The bioavailability of the drug cannot be compromised to meet patient compliance.
  • abiraterone as an active pharmaceutical agent used for treating prostate cancer, would be, preferred in a low dose oral composition provided in such a dosage form which exhibit desired therapeutic effect and at the same time would ensure patient compliance.
  • a low dose orally dispersible composition of abiraterone when designed was considered as the best approach, as these compositions could be dispersed in water and then easily administered by the patient and thus are advantageous for use in elder and noncompliant cancer patients.
  • the present invention provides a pharmaceutical composition comprising abiraterone and one or more pharmaceutically acceptable excipients, which is intended to ensure patient compliance due to simplification of therapy.
  • abiraterone is used in broad sense to include not only "abiraterone” per se but also its pharmaceutically acceptable derivatives thereof.
  • Suitable derivatives include pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable isomers, pharmaceutically acceptable esters, pharmaceutically acceptable anhydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable tautomers and/or pharmaceutically acceptable complexes thereof.
  • the pharmaceutical composition of the present invention comprises abiraterone in the form of abiraterone acetate.
  • low dose refers to a therapeutically effective dose of abiraterone, which dose is less than the usual or the conventional dose required to produce equal or higher therapeutic effect.
  • the term “low dose” means a total daily dose of abiraterone of less than 1000 mg per day.
  • pharmaceutical composition includes oral dosage forms, such as but not limited to, tablets, soft gelatin capsule, capsules (filled with powders, powders for reconstitution, pellets, beads, mini-tablets, pills, micro-pellets, small tablet units, multiple unit pellet system (MUPS), disintegrating tablets, dispersible tablets, granules, sprinkles microspheres and multiparticulates), sachets (filled with powders, pellets, beads, mini-tablets, pills, micro-pellets, small tablet units, MUPS, disintegrating tablets, dispersible tablets, granules, sprinkles microspheres and multiparticulates) and sprinkles.
  • oral dosage forms such as but not limited to, tablets, soft gelatin capsule, capsules (filled with powders, powders for reconstitution, pellets, beads, mini-tablets, pills, micro-pellets, small tablet units, multiple unit pellet system (MUPS), disintegrating tablets, dispersible tablets, granules, sprinkles microspheres and multiparticulates), sachets (filled
  • oral liquid dosage forms liquids, liquid dispersions, suspensions, solutions, emulsions, syrups, elixirs
  • oral liquid dosage forms liquids, liquid dispersions, suspensions, solutions, emulsions, syrups, elixirs
  • the pharmaceutical composition is a single unit dosage form. More preferably, the pharmaceutical composition is a single unit dosage form adapted for once daily administration.
  • the pharmaceutical composition of the present invention comprising abiraterone is in the form of a tablet. More preferably, the pharmaceutical composition of the present invention comprising abiraterone is in the form of an oral disintegrating tablet, disintegrating tablet or dispersing tablet, for example a tablet that dissolves in water.
  • the pharmaceutical composition of the present invention preferably comprises less than 1000 mg of abiraterone, more preferably from about 125 mg to about 800 mg of abiraterone.
  • a pharmaceutical composition comprising abiraterone with one or more pharmaceutically acceptable excipients wherein composition is formulated to provide a total daily dose of abiraterone of less than 1000 mg, preferably from about 125 mg to about 800 mg.
  • the pharmaceutical composition may be administered at least once a day.
  • the pharmaceutical composition is administered once a day.
  • the daily dose is preferably less than the conventionally administered dose, more preferably from about 300 mg to about 800 mg of abiraterone, still more preferably from about 175 mg to about 800 mg, and most preferably from about 125 mg to about 800 mg of abiraterone.
  • the composition is formulated to be administered as a single daily dose.
  • the pharmaceutical composition of the present invention may be administered with or without food. More preferably, the composition does not exhibit a food effect.
  • the inventors of the present invention have also further observed that the solubility properties of abiraterone are improved by nanosizing, thus leading to better bioavailability of the drug.
  • Nanonization of hydrophobic or poorly water-soluble drugs generally involves the production of drug nanocrystals through either chemical precipitation (bottom-up technology) or disintegration (top-down technology). Different methods may be utilized to reduce the particle size of the hydrophobic or poorly water soluble drugs. [Huabing Chen et ah, discusses the various methods to develop nanoformulations in "Nanonization strategies for poorly water-soluble drugs," Drug Discovery Today, Volume 00, Number 00, March 2010].
  • the present invention thus provides a pharmaceutical composition comprising abiraterone wherein abiraterone is in the nanosize range.
  • nanosize refers to abiraterone particles having an average particle size of less than or equal to about 2000 nm, preferably less than or equal to about 1000 nm. Usually all of the particles have a particle size of less than or equal to about 2000 nm, preferably less than or equal to about 1000 nm. Preferably, the particle size of abiraterone varies with D 0 not less than or equal to 700 nm, more preferably less than or equal to 300 nm.
  • particles refers to individual particles of abiraterone, or particles of abiraterone granules and/or mixtures thereof.
  • the nanosize particles of the present invention can be obtained by any of the process such as but not limited to milling, precipitation, homogenization, high pressure homogenization, spray- freeze drying, supercritical fluid technology, double emulsion/solvent evaporation, PRINT (Particle replication in non-wetting templates), thermal condensation, ultrasonication, spray drying or the like. Such nanoparticles obtained by any of these processes may further be formulated into desired dosage forms.
  • the nanoparticles of the abiraterone are preferably prepared by:
  • the process comprises a wet milling step.
  • the process does not include a dry milling step.
  • the present invention provides a process for preparing a pharmaceutical composition, which process comprises which process comprises admixing one or more pharmaceutically acceptable excipients with abiraterone.
  • the pharmaceutical composition of the present invention in the form of an orally disintegrating tablet that can be prepared by any of the processes such as freeze drying/lyophilization, moulding, sublimation, spray drying, mass extrusion and direct compression or the like.
  • Suitable excipients may be used for formulating the tablet dosage form according to the present invention such as, but not limited to, disintegrants, diluents, plasticizers, binders, glidants, lubricants, sweeteners, flavoring agents, antioxidants , texture enhancers , viscosity modifying agents , polymers , channeling agents , anti-caking agents, anti-microbial agents, antifoaming agents, emulsifiers, surfactants, buffering agents and coloring agents and combinations thereof.
  • Suitable disintegrants or super disintegrants include, but are not limited to, agar-agar, calcium carbonate, microcrystalline cellulose, crospovidone, povidone, polacrilin potassium, sodium starch glycolate, potato or tapioca starch, other starches, pre-gelatinized starch, clays, alginic acid, alginates such as sodium alginate other algins, other celluloses, gums, ion-exchange resins, magnesium aluminum silicate, sodium dodecyl sulfate, sodium carboxymethyl cellulose, croscarmellose sodium, polyvinylpyrollidone, cross-linked PVP, carboxymethyl cellulose calcium, crosslinked sodium carboxymethyl cellulose, docusate sodium, guar gum, low- substituted HPC, polacrilin potassium, poloxamer, povidone, sodium glycine carbonate and sodium lauryl sulfate or mixtures thereof.
  • the amount of disintegrant in the pharmaceutical compositions may range from
  • Suitable binders may also present in the in the pharmaceutical compositions of the present invention, which may comprise one or more, but not limited to polyvinyl pyrrolidone (also known as povidone), polyethylene glycol(s), acacia, alginic acid, agar, calcium carragenan, cellulose derivatives such as ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, dextrin, gelatin, gum arabic, guar gum, tragacanth, sodium alginate, or mixtures thereof or any other suitable binder.
  • polyvinyl pyrrolidone also known as povidone
  • polyethylene glycol(s) polyethylene glycol(s)
  • acacia alginic acid
  • agar calcium carragenan
  • cellulose derivatives such as ethyl cellulose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, sodium
  • the amount of binder in the pharmaceutical compositions may range from about 5% w/w to about 20% w/w of the total weight of the composition.
  • Suitable carriers, diluents or fillers for use, in the pharmaceutical composition of the present invention may comprise one or more, but not limited to lactose (for example, spray-dried lactose, a-lactose, ⁇ -lactose) lactose available under the trade mark Tablettose, various grades of lactose available under the trade mark Pharmatose or other commercially available forms of lactose, lactitol, saccharose, sorbitol, mannitol, dextrates, dextrins, dextrose, maltodextrin, croscarmellose sodium, microcrystalline cellulose (for example, microcrystalline cellulose available under the trade mark Avicel), hydroxypropylcellulose, L-hydroxypropylcellulose (low substituted), hydroxypropyl methylcellulose (HPMC), methylcellulose poly
  • the amount of carriers, diluents or fillers in the pharmaceutical compositions may range from about 15% w/w to about 60 % w/w of the total weight of the composition.
  • Glidants, anti-adherents and lubricants may also be incorporated in the pharmaceutical composition of the present invention, which may comprise one or more, but not limited to stearic acid and pharmaceutically acceptable salts or esters thereof (for example, magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate or other metallic stearate), talc, waxes (for example, microcrystalline waxes) and glycerides, mineral oil, light mineral oil, PEG, silica acid or a derivative or salt thereof (for example, silicates, silicon dioxide, colloidal silicon dioxide and polymers thereof, crospovidone, magnesium aluminosilicate and/ or magnesium alumino metasilicate), sucrose ester of fatty acids, hydrogenated vegetable oils (for example, hydrogenated cast
  • the amount of glidants, anti-adherents and lubricants in the pharmaceutical compositions may range from about 0.1% w/w to about 5 % w/w of the total weight of the composition.
  • Anti-caking agents may also be incorporated in the pharmaceutical composition of the present invention. Suitable anti-caking additives include, but are not limited to, calcium silicate, magnesium silicate, silicon dioxide, colloidal silicon dioxide, talc, or mixtures thereof.
  • Anti-microbial agents and/or preservatives may also be incorporated in the pharmaceutical composition of the present invention.
  • Suitable anti-microbial agents and/or preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzoic acid, benzyl alcohol, butyl paraben, cetylpyridinium chloride, cresol, chlorobutanol, dehydroacetic acid, ethylparaben, methylparaben, phenol, phenylethyl alcohol, phenoxyethanol, phenylmercuric acetate, phenylmercuric nitrate, potassium sorbate, propylparaben, sodium benzoate, sodium dehydroacetate, sodium propionate, sorbic acid, citric acid, tartaric acid, lactic acid, malic acid, acetic acid, benzoic acid, thimersol, thymo, or mixtures thereof.
  • Sweetening agents may also be incorporated in the pharmaceutical composition of the present invention.
  • suitable sweetening agent or taste-masking agents include, but are not limited to, essential oils, water soluble extracts, sugar (natural or synthetic), monosaccharides, oligosaccharides, aldose, ketose, dextrose, maltose, lactose, glucose, fructose, sucrose, mannitol xylitol, D-sorbitol, erythritol, pentitol, hexitol, malitol, acesulfame potassium, talin, glycyrrhizin, sucralose, aspartame, saccharin, sodium saccharin, acesulfame, thaumatin, dihydrochalcone, alitame, miraculin, monellin, stevside sodium cyclamate, eugenyl formate aldehyde flavorings or mixtures thereof.
  • Suitable flavors/flavouring agents which may be used in the pharmaceutical composition of the present invention include, but are not limited to, essential oils including distillations, solvent extractions, or cold expressions of chopped flowers, leaves, peel or pulped whole fruit containing mixtures of alcohols, esters, aldehydes and lactones; essences including either diluted solutions of essential oils, or mixtures of synthetic chemicals blended to match the natural flavor of the fruit (e.g., strawberry, raspberry and black currant); artificial and natural flavors of brews and liquors, e.g., cognac, whisky, rum, gin, sherry, port, and wine; tobacco, coffee, tea, cocoa, and mint; fruit juices including expelled juice from washed, scrubbed fruits such as lemon, orange, and lime; spear mint, pepper mint, wintergreen, cinnamon, cacoe/cocoa, vanilla, liquorice, menthol, eucalyptus, aniseeds nuts (e.g., peanuts, coconuts, hazelnuts, chestnut
  • Suitable antioxidants which may be used in the pharmaceutical composition of the present invention include, but are not limited to, tocopherols, ascorbic acid, sodium pyrosulfite, butylhydroxytoluene, butylated hydroxyanisole, edetic acid, and edetate salts, or mixtures thereof.
  • Suitable texture enhancers which may be used in the pharmaceutical composition of the present invention include, but are not limited to, pectin, polyethylene oxide, and carrageenan, or mixtures thereof.
  • Surface stabilizers are surfactants that are capable of stabilizing the increased surfaced charge drug. Suitable amphoteric, non-ionic, cationic or anionic surfactants may be included in the pharmaceutical composition of the present invention.
  • Suitable surfactants which may be used in the pharmaceutical composition of the present invention may comprise of one or more, but not limited to Polysorbates, Sodium dodecyl sulfate (sodium lauryl sulfate), Lauryl dimethyl amine oxide, Docusate sodium, Cetyl trimethyl ammonium bromide (CTAB)
  • Polyethoxylated alcohols Polyoxyethylene sorbitan, Octoxynol, N, N-dimethyldodecylamine- N-oxide, Hexadecyltrimethylammonium bromide, Polyoxyl 10 lauryl ether, Brij, Bile salts (sodium deoxycholate, sodium cholate), Polyoxyl castor oil, Nonylphenol ethoxylate Cyclodextrins, Lecithin, Methylbenzethonium chloride.
  • Carboxylates Sulphonates, Petroleum sulphonates, alkylbenzenesulphonates, Naphthalenesulphonates, Olefin sulphonates, Alkyl sulphates, Sulphates, Sulphated natural oils & fats, Sulphated esters, Sulphated alkanolamides, Alkylphenols, ethoxylated & sulphated, Ethoxylated aliphatic alcohol, polyoxyethylene surfactants, carboxylic esters Polyethylene glycol esters, Anhydrosorbitol ester and its ethoxylated derivatives, Glycol esters of fatty acids, Carboxylic amides, Monoalkanolamine condensates, Polyoxyethylene fatty acid amides, Quaternary ammonium salts, Amines with amide linkages, Polyoxyethylene alkyl & alicyclic amines, ⁇ , ⁇ , ⁇ , ⁇ tetrakis substituted ethylenediamines 2- alkyl 1-
  • the amount of surfactant in the pharmaceutical compositions may range from about 2% w/w to about 10% w/w of the total weight of the composition.
  • Viscosity modifying agents are excipients that are capable of stabilizing the formulation by increasing the viscosity of the formulation and thus preventing physical interaction of nanoparticles under the operating conditions employed.
  • the amount of viscosity modifying agents in the pharmaceutical compositions may range from about 4% w/w to about 20% w/w of the total weight of the composition.
  • Viscosity modifying agents which may be used in the pharmaceutical composition of the present invention may comprise one or more, but not limited to derivatives of sugars, such as lactose, sucrose, saccharose, hydrolyzed starch (maltodextrin) or mixtures thereof
  • a preferred viscosity modifying agent is lactose.
  • Polymers or polymers blends which may be used in the pharmaceutical composition of the present invention, may comprise one or more hydrophilic polymers, but not limited to cellulose derivates like hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose polymers hydroxyethylcellulose, sodium carboxymethylcellulose, carboxymethylene and carboxymethyl hydroxyethylcellulose; acrylics like acrylic acid, acrylamide, and maleic anhydride polymers, acacia, gum tragacanth, locust bean gum, guar gum, or karaya gum, agar, pectin, carrageenan, gelatin, casein, zein and alginates, carboxypolymethylene, bentonite, magnesium aluminum silicate, polysaccharides, modified starch derivatives and copolymers or mixtures thereof.
  • hydrophilic polymers but not limited to cellulose derivates like hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, methylcellulose polymers
  • the amount of polymers or polymers blends in the pharmaceutical compositions range from about 2% w/w to about 15% w/w, of the total weight of the composition.
  • Suitable channeling agents for use in compositions of the invention may comprise one or more, but are not limited to sodium chloride, sugars, polyols and the like or mixtures thereof.
  • the channeling agents may be present in an amount ranging from about 0.5% to about 10% by weight of the composition.
  • the pharmaceutical composition of the present invention may further comprise at least one additional active pharmaceutical ingredient such as, but not limited to, prednisone and dutasteride, or a pharmaceutically acceptable derivatives thereof.
  • the present invention also provides a method of treating prostate cancer by administering a pharmaceutical composition of abiraterone.
  • the present invention also provides a method of treating prostate cancer by administering a pharmaceutical composition of abiraterone in combination with prednisone.
  • the present invention also provides abiraterone for use in the treatment of prostate cancer, wherein the total daily dose of the abiraterone is less than 1000 mg, preferably from about 125 mg to about 800 mg, and wherein abiraterone is administered as a single daily dose.
  • the present invention also provides a method of treating prostate cancer by administering a pharmaceutical composition of abiraterone in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
  • the present invention also provides the use of the pharmaceutical composition comprising abiraterone for treating prostate cancer.
  • the present invention also provides the use of the pharmaceutical composition comprising abiraterone for treating prostate cancer in combination with prednisone.
  • the present invention also provides the use of the pharmaceutical composition comprising abiraterone for treating prostate cancer in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
  • step (3) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate.
  • step (2) Abiraterone Acetate was dispersed in the solution obtained in step (1) and then milled to form a slurry.
  • step (3) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate.
  • step (2) Abiraterone Acetate was dispersed in the solution obtained in step (1) and then milled to form a slurry.
  • step (3) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate.
  • step (2) Abiraterone Acetate was dispersed in the solution obtained in step (1) and then milled to form a slurry.
  • step (3) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate. D) Compression:
  • step (4) The lubricated granules obtained in step (4) were compressed to form dispersible tablets
  • step (3) Lactose and crospovidone were sprayed onto the slurry in step (2) and granulated.
  • step (3) Blending & Lubrication: 4) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate.
  • step (4) The lubricated granules obtained in step (4) were compressed to form dispersible tablets
  • step (2) Abiraterone Acetate was dispersed in the solution obtained in step (1) and then milled to form a slurry.
  • step (3) The granules obtained in step (3) were blended and lubricated with crospovidone, silicified microcrystalline cellulose, sodium Chloride and magnesium stearate.
  • step (4) The lubricated granules obtained in step (4) were compressed to form dispersible tablets.
  • step (3) The mixture obtained in step (1) was granulated with the binder solution obtained in step (2).
  • step (3) Blending & Lubrication:
  • step (3) The granules obtained in step (3) were dried, blended and lubricated with croscarmellose sodium, colloidal silicon dioxide and magnesium stearate.

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018037310A1 (en) * 2016-08-20 2018-03-01 Ftf Pharma Private Limited Pharmaceutical composition comprising an androgen receptor inhibitor
WO2019206472A1 (en) * 2018-04-26 2019-10-31 Synthon B.V. Tablet compositions comprising abiraterone acetate
WO2020126017A1 (en) * 2018-12-20 2020-06-25 Pharmaceutical Oriented Services Ltd Dosage form containing abiraterone acetate
US10722527B2 (en) 2015-04-10 2020-07-28 Capsugel Belgium Nv Abiraterone acetate lipid formulations
CN113384532A (zh) * 2020-03-14 2021-09-14 鲁南制药集团股份有限公司 一种cyp17抑制剂固体分散体及其制备方法
EP3944860A1 (en) * 2020-07-30 2022-02-02 Galenicum Health S.L.U. Abiraterone for use in a method of treating cancer
CN115135313A (zh) * 2019-10-22 2022-09-30 阿维纳斯企业公司 治疗前列腺癌的方法
CN115475172A (zh) * 2021-06-15 2022-12-16 北京泰德制药股份有限公司 一种含有阿比特龙或其药用盐的药用组合物
EP3999040A4 (en) * 2019-07-15 2023-07-19 Shilpa Medicare Limited DISPERSABLE TABLETS OF ABIRATERONACETATE
US11952347B2 (en) 2016-10-11 2024-04-09 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US12043612B2 (en) 2020-05-09 2024-07-23 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
US12403149B2 (en) 2019-07-15 2025-09-02 Shilpa Medicare Limited Dispersible tablets of abiraterone acetate

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012042224A2 (en) * 2010-10-01 2012-04-05 Cipla Limited Pharmaceutical composition
WO2013164473A1 (en) * 2012-05-04 2013-11-07 Jagotec Ag Pharmaceutical composition comprising abiraterone acetate
WO2014009436A1 (en) * 2012-07-11 2014-01-16 Sandoz Ag Nanosuspension of abiraterone acetate
WO2014145813A1 (en) * 2013-03-15 2014-09-18 Iceutica Inc. Abiraterone acetate formulation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012042224A2 (en) * 2010-10-01 2012-04-05 Cipla Limited Pharmaceutical composition
WO2013164473A1 (en) * 2012-05-04 2013-11-07 Jagotec Ag Pharmaceutical composition comprising abiraterone acetate
WO2014009436A1 (en) * 2012-07-11 2014-01-16 Sandoz Ag Nanosuspension of abiraterone acetate
WO2014145813A1 (en) * 2013-03-15 2014-09-18 Iceutica Inc. Abiraterone acetate formulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HUABING CHEN ET AL: "Nanonization strategies for poorly water-soluble drugs", DRUG DISCOVERY TODAY, vol. 16, no. 7, April 2011 (2011-04-01), pages 354 - 360, XP028187050, ISSN: 1359-6446, [retrieved on 20100303], DOI: 10.1016/J.DRUDIS.2010.02.009 *

Cited By (18)

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US10722527B2 (en) 2015-04-10 2020-07-28 Capsugel Belgium Nv Abiraterone acetate lipid formulations
WO2018037310A1 (en) * 2016-08-20 2018-03-01 Ftf Pharma Private Limited Pharmaceutical composition comprising an androgen receptor inhibitor
US11952347B2 (en) 2016-10-11 2024-04-09 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US12077509B2 (en) 2016-10-11 2024-09-03 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
US11964945B2 (en) 2016-10-11 2024-04-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
WO2019206472A1 (en) * 2018-04-26 2019-10-31 Synthon B.V. Tablet compositions comprising abiraterone acetate
US11865215B2 (en) 2018-04-26 2024-01-09 Synthon B.V. Tablet compositions comprising abiraterone acetate
WO2020126017A1 (en) * 2018-12-20 2020-06-25 Pharmaceutical Oriented Services Ltd Dosage form containing abiraterone acetate
AU2018454263B2 (en) * 2018-12-20 2024-02-15 Pharmaceutical Oriented Services Ltd Dosage form containing abiraterone acetate
US12403149B2 (en) 2019-07-15 2025-09-02 Shilpa Medicare Limited Dispersible tablets of abiraterone acetate
EP3999040A4 (en) * 2019-07-15 2023-07-19 Shilpa Medicare Limited DISPERSABLE TABLETS OF ABIRATERONACETATE
CN115135313A (zh) * 2019-10-22 2022-09-30 阿维纳斯企业公司 治疗前列腺癌的方法
CN113384532A (zh) * 2020-03-14 2021-09-14 鲁南制药集团股份有限公司 一种cyp17抑制剂固体分散体及其制备方法
CN113384532B (zh) * 2020-03-14 2024-03-29 鲁南制药集团股份有限公司 一种cyp17抑制剂固体分散体及其制备方法
US12043612B2 (en) 2020-05-09 2024-07-23 Arvinas Operations, Inc. Methods of manufacturing a bifunctional compound, ultrapure forms of the bifunctional compound, and dosage forms comprising the same
EP3944860A1 (en) * 2020-07-30 2022-02-02 Galenicum Health S.L.U. Abiraterone for use in a method of treating cancer
CN115475172B (zh) * 2021-06-15 2023-12-01 北京泰德制药股份有限公司 一种含有阿比特龙或其药用盐的药用组合物
CN115475172A (zh) * 2021-06-15 2022-12-16 北京泰德制药股份有限公司 一种含有阿比特龙或其药用盐的药用组合物

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