WO2013175493A1 - Compositions pharmaceutiques orales stables - Google Patents

Compositions pharmaceutiques orales stables Download PDF

Info

Publication number
WO2013175493A1
WO2013175493A1 PCT/IN2013/000234 IN2013000234W WO2013175493A1 WO 2013175493 A1 WO2013175493 A1 WO 2013175493A1 IN 2013000234 W IN2013000234 W IN 2013000234W WO 2013175493 A1 WO2013175493 A1 WO 2013175493A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
rasagiline
stable pharmaceutical
salts
pharmaceutically acceptable
Prior art date
Application number
PCT/IN2013/000234
Other languages
English (en)
Inventor
Sunilendu Bhushan Roy
Sushrut Krishnaji Kulkarni
Maulik Kiritkumar Panchal
Original Assignee
Cadila Healthcare Limited
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 Cadila Healthcare Limited filed Critical Cadila Healthcare Limited
Publication of WO2013175493A1 publication Critical patent/WO2013175493A1/fr

Links

Classifications

    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • 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
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin

Definitions

  • the present invention relates to pharmaceutical compositions of rasagiline, its enantiomer or salts thereof.
  • the invention relates to stable pharmaceutical compositions of rasagiline, its enantiomer or salts thereof, process of preparation of such compositions and use thereof for treatment of Parkinson's disease, Dementia and Alzheimer's disease.
  • Rasagiline is a selective irreversible inhibitor of monoamine oxidase enzyme Type-B (MAO-B) and has the chemical name N-propargyl-l (R)-aminoindan (“(R)-PAI"). Its structural formula is:
  • Rasagiline is an active MAO-B inhibitor while the corresponding S-enantiomer
  • (S)-Rasagiline shows extremely low MAO-B inhibitory activity (U.S. Patent No. 6,316,504). It has also been found that (R)-Rasagiline has a degree of selectivity for MAO-B inhibition surprisingly higher than that of the corresponding racemic form (U.S. Patent No. 6,316,504). The fact that (R)-Rasagiline is more active than the racemic mixture for the inhibition of MAO-B is a reflection of the extremely low activity of (S)- Rasagiline for inhibition of MAO-B (U.S. Patent No. 6,316,504).
  • Rasagiline its salts, preparation and use for the treatment of Parkinson's disease, Alzheimer's disease, memory disorders, stroke and other disorders have been the subject of numerous patents, including U.S. Patent Nos. 5,387,612, 5,453,446, 5,457, 133, 5,668,181, 5,576,353, 5,532,415, 5,599,991 , 5,786,390, 5,519,061, 5,891 ,923, 5,744,500 and 6,316,504, the contents of which are hereby incorporated by reference.
  • Rasagiline is currently marketed in US in the form of film coated tablets under trade name Azilect® by Teva Pharmaceuticals.
  • PCT publication No. WO 95/1 1016 discloses pharmaceutical formulations of rasagiline.
  • European Patent No. EP 0814789 discloses formulations of MAO-B inhibitors which attempt to address some of the known problems.
  • the European patent relies on lyophilization of the MAO-B inhibitor formulations which is a costly process and results in high friability of the product, further increasing cost by necessitating costly special blister-pack packaging.
  • PCT Publication No. WO 2010/1 1 1264 discloses pharmaceutical formulations comprising rasagiline, or a pharmaceutically acceptable salt thereof with a particle size distribution wherein about 90% of the particles have particle sizes smaller than 1000 ⁇ , and having content uniformity such that the formulation contains 90% to 1 10% of the label content of rasagiline or its salt, wherein the formulations are substantially free of a sugar alcohol.
  • PCT publication No. WO 201 1/010324 discloses stable rasagiline compositions comprising rasagiline or its salts and a carrier selected from poly hydric alcohol, disaccharide(s) and poly saccharide(s) or mixtures thereof, and wherein the said composition is free of pentahydric or hexa hydric alcohols.
  • EP 1892233 discloses polymorphic forms of rasagiline oxalate and rasagiline edisilate.
  • the patent application also discloses that mesylate, hydrochloride and phosphate salts of rasagiline show agglomerates after storage even in a closed glass bottle and can also display a slight discoloration and when stored under humid conditions (40°C, 75% relative humidity in an open glass bottle), a sticky powder which is difficult to process forms from said salts of rasagiline.
  • Different salt forms of the same pharmaceutically active moiety differ in their physical properties such as melting point, solubility, chemical reactivity, stability etc. These properties may appreciably influence pharmaceutical properties such as dissolution rate and bioavailability.
  • Polymorphism is very common among pharmaceutical substances. It is commonly defined as the ability of any substance to exist in two or more crystalline phases that have a different arrangement and/or conformation of the molecules in the crystal lattice.
  • a stable pharmaceutical composition comprising rasagiline, its enantiomer or salts thereof and atleast one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols.
  • a stable pharmaceutical composition comprising rasagiline besylate or its enantiomer and atleast one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols.
  • a stable pharmaceutical composition comprising rasagiline hydrogen phosphate or its enantiomer and atleast one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols.
  • a stable pharmaceutical composition comprising rasagiline, its enantiomer or salts thereof and atleast one antioxidant.
  • a stable pharmaceutical composition comprising rasagiline, its enantiomer or salts thereof and atleast one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols, wherein said composition retains at least 80% of the potency of rasagiline, its enantiomer or salts thereof in the pharmaceutical composition after storage for three months at 40° C and 75% relative humidity.
  • a pharmaceutical packaging kit comprising a sealed oxygen impermeable container comprising a pharmaceutical composition comprising rasagiline crampHs enantiomer or salts thereof and at least one pharmaceutically acceptable stabilizer selected from the group consisting of an oxygen absorber, a moisture absorber or a combination thereof.
  • a pharmaceutical kit comprising a container having deposited therein rasagiline, its enantiomer or salts thereof in a solid unit dosage form and at least one oxygen absorber (preferably a self-activated absorber).
  • the oxygen absorber may be provided in a sachet, cartridge, canister or any other means of containing the absorber such that the absorber is physically separated from the solid dosage forms deposited in the container and has sufficient oxygen permeability to remove at least a portion of the oxygen in the air within the container.
  • the sealed oxygen permeable container may also include a desiccant.
  • a stable pharmaceutical composition comprising a pharmaceutical formulation comprising rasagilinenapsits enantiomer or salts thereof and at least one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols, and a packing not permeable to gas exchange, wherein the formulation is enveloped in the packaging under an inert gas atmosphere, said composition produced by the process of-
  • a method of stablization of pharmaceutical composition comprising a pharmaceutical formulation comprising rasagilinenapsits enantiomer or salts thereof and atleast one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols, the method comprising packing the pharmaceutical formulation into packing not permeable to gas exchange, wherein the packaging step is carried out in an inert gas atmosphere, and enveloping the formulation in the inert gas atmosphere.
  • a stable pharmaceutical composition of rasagiline, its enantiomer or salt thereof comprising at least one stabilizer, at least one water soluble and/or water insoluble polymer and pharmaceutical excipients comprising disintegrating agents, diluents, fillers, binders, lubricants, glidants, sweeteners and flavors, wherein said composition is free of sugar alcohols or polyols.
  • the pharmaceutical composition may further include one or more pharmaceutical acceptable excipients.
  • the pharmaceutical acceptable excipients may include fillers/diluents, binders, polymers, disintegrants, stabilizers, lubricants, glidants, sweeteners, taste masking agents and flavors.
  • a pharmaceutical composition comprising rasagiline, its enantiomer or salts thereof and at least one stabilizer, wherein rasagiline, its enantiomer or salts thereof have 90th volume percentile particle size (D90) greater than about 250 ⁇ , or any combination thereof.
  • D90 volume percentile particle size
  • rasagiline, its enantiomer or salts thereof may have particle size distribution wherein 10th volume percentile particle size (D10) is greater than about 20 ⁇ , the 50th volume percentile particle size (D50) is greater than about 100 ⁇ , D(90) is greater than about 250 ⁇ , or any combination thereof.
  • a method of treating Parkinson's disease, dementia and Alzheimer's disease in patient comprising administering to said subject a pharmaceutical composition comprising rasagiline, its enantiomer or salts thereof comprising atleast one pharmaceutically acceptable stabilizer, and one or more pharmaceutical excipients, wherein said composition is free of sugar alcohols or polyols.
  • a stable pharmaceutical composition of rasagiline comprising rasagiline, its enantiomer or salts thereof and atleast one antioxidant.
  • the inventors of the present invention have also found that the stability of pharmaceutical composition of rasagiline comprising rasagiline, its enantiomer or salts thereof can be significantly improved by packing the formulation with oxygen absorber or using a packing not permeable to gas exchange, or envelpoing the composition in the packaging under an inert gas atmosphere, without employing any sugar alcohols or polyols.
  • oxygen absorbers means agents used to trap oxygen that is present in the overhead space of closed container. Concerning the chemical and physical mechanisms of active oxygen absorbers* they can be classified into the following categories:
  • Polymer based scavengers are suitable for moisture protected applications.
  • Polymer-based compounds consist of high molecular weight, ethylenically-unsaturated hydrocarbons. An activation step often enables the user to start the oxygen scavenging when desired.
  • sachets include D Series FreshPaxTM (available from Multisorb Technologies Inc), AgelessTM Z (Ageless-Z is designated as Z-IOO, Z-1000, etc., to indicate the milliliters of oxygen with which a single packet will react), StabilOx D (available from Multisorb Technologies Inc) and ZPTJTM sachets (both available from Mitsubishi Gas Corporation), O-BusterTM (available from Hsiao Sung Non-Oxygen Chemical Co., Ltd), BiokaTM Oxygen Absorber (available from Bioka Ltd) and the like.
  • the moisture absorbers include activated carbon, silicas, zeolites, molecular sieves, hydrogels, calcium oxide and diatomaceous earth.
  • the particular moisture - retaining materials used will depend upon the humidity level of the environment. For example, in a very low-humidity environment, a moisture-carrying material such as a hydrogel that partially binds water may be preferred.
  • the moisture absorber can be supplied in the form of a sachet, cartridge or canister.
  • a preferred form is a canister of silica gel, such as SorBitTM (commercially supplied by Sud-Chemie Corporation).
  • Multisorb provides variety of moisture absorbers under trade name of Natrasorb M, Natrasorb S, Natrasorb C, and Hi-dry, which comprise diatomaceous earth, silica gel, calcium oxide and molecular sieve, respectively.
  • packets or sachets which comprise a combination of oxygen absorber and moisture absorber such as Pharmakeep oxygen- and moisture-absorbing packets (PharmaKeep KD or KC) (distributed jointly by Sud-Chemie and Mitsubishi Gas Chemical Company).
  • Pharmakeep oxygen- and moisture-absorbing packets PharmaKeep KD or KC
  • the moisture/oxygen absorber may be in the form of packet, sachet, strips or canisters.
  • the packet, sachet, strips or canisters may additionally comprise a moisture- indicating card.
  • the pharmaceutical kit comprising a sealed oxygen permeable container (preferably sealed with a heat-induction seal (HIS)) having deposited therein rasagiline, its enantiomer or salts thereof in a solid unit dosage form and at least one oxygen absorber (preferably a self-activated absorber).
  • a sealed oxygen permeable container preferably sealed with a heat-induction seal (HIS)
  • HIS heat-induction seal
  • the oxygen absorber may be provided in a sachet, cartridge, canister (preferably a cartridge) or any other means of containing the absorber such that the absorber is physically separated from the solid dosage forms deposited in the container and has sufficient oxygen permeability to remove at least a portion of the oxygen in the air within the container.
  • the sealed oxygen permeable container may also include a desiccant.
  • the desiccant for use in the practice of the invention can be any available desiccants; however, preferred desiccants include those commonly used in the pharmaceutical industry which have adequate capacity to handle the combination of moisture ingress through the container (e.g. glass or plastic bottle) and moisture given off by the self-activating oxygen absorber. Suitable desiccant are discussed in R. L. Dobson, J. Packaging Technol., 1 , 127-131 (1987).
  • a preferred desiccant is silica gel.
  • the desiccant can be supplied in the form of a sachet, cartridge or canister.
  • a preferred form for the practice of the current invention is a canister of silica gel, such as that commercially supplied under the trade name, SorBit.TM. (Sud-Chemie Corporation, Albuquerque, N.Mex.).
  • the inventions provides a stable pharmaceutical composition
  • a pharmaceutical formulation comprising rasagiline, its enantiomer or salts thereof and at least one pharmaceutically acceptable stabilizer other than sugar alcohols or polyols, and a packing not permeable to gas exchange, wherein the formulation is enveloped in the packaging under an inert gas atmosphere, said composition produced by the process of -
  • the stabilizers of the present invention can be any available pharmaceutically acceptable stabilizer other than sugar alcohols or polyols, preferably antioxidant.
  • Suitable antioxidants are, but not limited to ascorbic acid, fumaric acid, citric acid, malic acid, gallic acid and its salts and esters, sodium metabisulphite, BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), vitamin E, vitamin E acetate, vitamin E PEG 1000 succinate, mixtures thereof and the like and the like.
  • the amount of antioxidant in the composition may range between about 0.1% w/w to about 10% w/w of the composition or between about 0.5% w/w to about 5% w/w of the composition.
  • a pharmaceutical composition of rasagiline, its enantiomer or salts thereof comprising atleast one pharmaceutically acceptable stabilizer, wherein rasagiline, its enantiomer or salts thereof have 90th volume percentile particle size (D90) greater than about 250 ⁇ , or any combination thereof.
  • rasagiline, its enantiomer or salts thereof may have particle size distribution, wherein 10th volume percentile particle size (D10) is greater than about 20 ⁇ , the 50th volume percentile particle size (D50) is greater than about 100 ⁇ , and D(90) is greater than about 250 ⁇ , or any combination thereof.
  • rasagiline, its enantiomer or salts thereof may have particle size D(90) greater than 250 microns, and D(50) greater than 150 microns.
  • 'sugar alcohols' used hereinbefore and throughout the description hereinafter refers to polyhydric sugar and its derivatives e.g. lactose, mannitol, xylitol, fructose, maltitol, isomaltitol, erythritol, lactitol and Sorbitol and the term 'polyols' used hereinbefore and throughout the description hereinafter refers to excipients containing more that four alcohol (-OH) groups.
  • the pharmaceutical composition of rasagiline, its enantiomer or salts thereof can be prepared by any suitable method known in the art such as direct compression, dry or wet granulation, fluidized bed granulation, melt extrusion, melt granulation, spray coating, freeze drying, spray drying and solution evaporation.
  • direct compression is preferred when formulations of phosphate salt of rasagiline is developed.
  • the process of preparing the pharmaceutical composition of rasagiline, its enantiomer or salts thereof comprises admixing the rasagiline, its enantiomer or salts thereof and stabilizer with water soluble and/or water insoluble polymer together with one or more pharmaceutical excipient and compressing into suitable dosage form, particularly solid dosage form such as tablets.
  • the pharmaceutical composition may be formulated into orally disintegrating tablets, pellets, wafers, granules, micro-granules, powders, capsules, tablets, lozenges, films, chewables, pellets in capsule, granules in capsule or any other dosage form suitable for oral administration.
  • the pharmaceutical composition's provided as a tablet which can be film coated with one or more coating agents.
  • Usable coating agents are hypromellose, polyvinyl alcohol, sodium carboxymethyl cellulose and various methacrylic acid polymers.
  • the coating may also contain further such as plasticizers, pigments, pore forming materials or suspension stabilizers, such as polyethylene glycol, talcum or titanium dioxide.
  • the composition of rasagiline, its enantiomer or salts thereof can be developed into fast-releasing and delayed-releasing compositions by methods known to the person skilled in the art.
  • compositions of rasagiline comprise one or more diluents, fillers/bulking agents, binders, disintegrants, lubricants, glidants, sweeteners/taste masking agents, colorants and flavors.
  • the pharmaceutically acceptable excipients for use in the pharmaceutical composition of rasagiline contains less than five alcohol (-OH) groups.
  • Suitable diluents/fillers or bulking agents which includes, but are not limited to, saccharides, including monosaccharides, disaccharides, polysaccharides and sugar alcohols having less than five alcohol (-OH) groups, dibasic calcium phosphate and other bulking agents such as powdered cellulose and derivatives thereof.
  • Suitable binders which includes, but are not limited to, cellulose derivatives, starch, polyvinyl pyrrolidone (PVP), gelatin, gum Arabic, polyvinyl alcohol, tragacanth, sodium alginate and equivalents thereof.
  • PVP polyvinyl pyrrolidone
  • Suitable disintegrants which includes, but are not limited to, croscarmellose sodium, crospovidone, sodium starch glycolate, corn starch, potato starch, maize starch and modified starches, calcium silicates, low substituted hydroxy- propylcellulose.
  • Suitable lubricants and glidants which may include, but are not limited to, stearic acid and its derivatives or esters like sodium stearate, magnesium stearate and calcium stearate and the corresponding esters such as sodium stearyl fumarate; talc and colloidal silicon dioxide.
  • Suitable taste masking agents may include one or more of polymers, surfactants, sweeteners and flavors.
  • polymers include one or more of cellulose acetate, polymethacrylates, cellulose derivatives such as hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxylethyl cellulose; and the like.
  • sweeteners include but not limiting to one or more of aspartame, saccharin, sucralose, glycyrrhizin; and the like.
  • Suitable sweeteners that may be used, comprises saccharides such as aspartame, sugar derivatives having less than five alcohol (-OH) groups.
  • Other examples of sweeteners comprise sodium saccharin; aspartame; sugarless sweeteners including glycerol, hydrogenated starch hydrolysates, alone or in combination.
  • Suitable flavors that may be used, comprise citric acid, cinnamon, wintergreen, eucalyptus, spearmint, peppermint, menthol, anise as well as fruit flavors such as apple, pear, peach, vanilla, strawberry, cherry, apricot, orange, watermelon, banana and the like; bean-derived flavors, such as coffee, cocoa and the like or mixtures thereof.
  • Drug solution was prepared by dissolving drug in Isopropyl Alcohol.
  • the drug solution was adsorbed onto mixture of Dibasic calcium phosphate anhydrous, Microcrystalline Cellulose & Pregelatinized Starch in rapid mixture granulator following by drying in fluidized bed dryer at temperature of about 60 °C.
  • Dried granules were sized through suitable screen following by blending with extra-granular Colloidal silicon dioxide and lubricating with stearic acid. Finally lubricated blend was compressed to form tablets and packed in Alu-Alu Blisters and charged for stability study.
  • Example 2 Example 2:
  • Drug solution was prepared by dissolving drug, ascorbic acid and Butylated Hydroxy Anisole in Isopropyl Alcohol.
  • the drug solution was adsorbed onto mixture of Dibasic calcium phosphate anhydrous & Pregelatinized Starch in rapid mixture granulator following by drying in fluidized bed dryer at temperature of about 60 °C.
  • Dried granules were sized through suitable screen following by blending with extra- granular Colloidal silicon dioxide and lubricating with stearic acid. Finally lubricated blend was compressed to form tablets and packed in Alu-Alu Blisters and charged for stability study.
  • Drug solution was prepared by dissolving drug in Isopropyl Alcohol.
  • the drug solution was adsorbed onto mixture of Dibasic calcium phosphate anhydrous, Pregelatinized Starch & Microcrystailine Cellulose in rapid mixture granulator following by drying in fluidized bed dryer at temperature of about 60 °C.
  • Dried granules were sized through suitable screen following by blending with extra-granular Colloidal silicon dioxide and lubricating with stearic acid. Finally lubricated blend was compressed to form tablets and packed in Alu-Alu Blisters and charged for stability study.
  • Drug solution was prepared by dissolving drug in purified water.
  • the drug solution was adsorbed onto mixture of Dibasic calcium phosphate dihydrate, Pregelatinized Starch & Microcrystailine Cellulose in rapid mixture granulator following by drying in fluidized bed dryer at temperature of about 60 °C.
  • Dried granules were sized through suitable screen following by blending with extra-granular Colloidal silicon dioxide and lubricating with stearic acid. Finally lubricated blend was compressed to form tablets and packed in Alu-Alu Blisters and charged for stability study.
  • Drug solution was prepared by dissolving drug, ascorbic acid and Butylated Hydroxy toluene in Isopropyl Alcohol.
  • the drug solution was adsorbed onto mixture of Dibasic calcium phosphate anhydrous & Pregeiatinized Starch in rapid mixture granulator following by drying in fluidized bed dryer at temperature of about 60 °C.
  • Dried granules were sized through suitable screen following by blending with extra- granular Colloidal silicon dioxide and lubricating with stearic acid. Finally lubricated blend was compressed to form tablets and packed in Alu-Alu Blisters and charged for stability study.
  • Samples of the formulation are packed in Alu-Alu Blisters and stored at the accelerated stability testing conditions of 40°C and 75% RH.
  • the impurity content is analyzed by HPLC at intervals and results are show below, where values are percentages of the rasagiline label content.

Landscapes

  • 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)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne des compositions pharmaceutiques de rasagiline, son énantiomère ou les sels de ceux-ci. En particulier, l'invention concerne des compositions pharmaceutiques stables de rasagiline, son énantiomère ou les sels de ceux-ci, et le procédé de préparation de telles compositions.
PCT/IN2013/000234 2012-04-09 2013-04-09 Compositions pharmaceutiques orales stables WO2013175493A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1147MU2012 2012-04-09
IN1147/MUM/2012 2012-04-09

Publications (1)

Publication Number Publication Date
WO2013175493A1 true WO2013175493A1 (fr) 2013-11-28

Family

ID=49036616

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2013/000234 WO2013175493A1 (fr) 2012-04-09 2013-04-09 Compositions pharmaceutiques orales stables

Country Status (1)

Country Link
WO (1) WO2013175493A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115400090A (zh) * 2022-10-09 2022-11-29 北京新领先医药科技发展有限公司 一种雷沙吉兰的口崩片组合物及其制备方法

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5387612A (en) 1990-01-03 1995-02-07 Teva Pharmaceutical Industries Ltd. Use of the R-enantiomers of N-propargyl-1-aminoindan compounds for treating Parkinson's disease
WO1995011016A1 (fr) 1993-10-18 1995-04-27 Teva Pharmaceutical Industries Ltd. R-enantiomere de n-propargyl-1-amino-indane, sels, compositions et utilisation de ce compose
EP0814789A1 (fr) 1995-03-02 1998-01-07 R.P. Scherer Limited Compositions pharmaceutiques comportant des inhibiteurs de monoamine-oxydase b
US5744500A (en) 1990-01-03 1998-04-28 Teva Pharmaceutical Industries, Ltd. Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof
US6126968A (en) 1995-09-20 2000-10-03 Teva Pharmaceutical Industries, Ltd. Stable compositions containing N-propargyl-1-aminoindan
EP1892233A1 (fr) 2006-08-18 2008-02-27 Ratiopharm GmbH De nouveaux sels de la substance active rasagiline
US20100137447A1 (en) * 2007-04-30 2010-06-03 Ratiopharm Gmbh Method for the production of adsorbates of a rasagiline salt having a water-soluble adjuvant
EP2218444A2 (fr) * 2009-01-23 2010-08-18 Teva Pharmaceutical Industries, Ltd. Formulation de rasagiline à libération retardée
WO2010111264A2 (fr) 2009-03-24 2010-09-30 Dr. Reddy's Laboratories Ltd. Préparations de rasagiline
WO2011010324A1 (fr) 2009-07-23 2011-01-27 Alkem Laboratories Ltd. Compositions pharmaceutiques orales stables comprenant de la rasagiline et procédé
EP2389927A1 (fr) * 2010-05-30 2011-11-30 Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi Formulations pharmaceutiques de rasagiline

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5744500A (en) 1990-01-03 1998-04-28 Teva Pharmaceutical Industries, Ltd. Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof
US5519061A (en) 1990-01-03 1996-05-21 Teva Pharmaceutical Industries Ltd. R-enantiomer of n-propargyl-1-aminoindan, salts, compositions and uses thereof
US5387612A (en) 1990-01-03 1995-02-07 Teva Pharmaceutical Industries Ltd. Use of the R-enantiomers of N-propargyl-1-aminoindan compounds for treating Parkinson's disease
US5891923A (en) 1990-01-03 1999-04-06 Teva Pharmaceutical Industries Ltd. R-enantiomer of N-propargyl-1-aminoindan for the treatment of dementia
US5786390A (en) 1990-01-03 1998-07-28 Teva Pharmaceutical Industries Ltd. Pharmaceutical compositions of the R-enantiomer of N-propargyl -1-aminoindan
US5532415A (en) 1990-01-03 1996-07-02 Teva Pharmaceutical Industries Ltd. R-enantiomer of N-propargyl-1-aminoindan, salts, compositions and uses thereof
US5576353A (en) 1990-01-03 1996-11-19 Teva Pharmaceutical Industries Ltd. Method of treating memory disorders using R-enantiomers of N-propargyl-aminoindan compounds
US5599991A (en) 1990-01-03 1997-02-04 Teva Pharmaceutical Industries Ltd. Esylate and sulfate salts of R(+)-N-propargyl-1-aminoindan
US5668181A (en) 1990-01-03 1997-09-16 Teva Pharmaceutical Industries Ltd. Use of the R-enantiomers of N-propargyl-1-aminoindan compounds for the treatment of depression
US5457133A (en) 1990-01-03 1995-10-10 Teva Pharmaceutical Industries Ltd. R-enantiomers of N-propargyl-aminoindan compounds, their preparation and pharmaceutical compositions containing them
US5453446A (en) 1990-01-03 1995-09-26 Teva Pharmaceutical Industries, Ltd. Use of the R-enantiomers of N-propargyl 1-aminoindan compounds for treating Parkinson's disease.
WO1995011016A1 (fr) 1993-10-18 1995-04-27 Teva Pharmaceutical Industries Ltd. R-enantiomere de n-propargyl-1-amino-indane, sels, compositions et utilisation de ce compose
US6316504B1 (en) 1993-10-18 2001-11-13 Technion Research And Development Foundation, Ltd. Use of R-enantiomer of N-propargyl-1-aminoindan, salts, and compositions thereof
EP0814789A1 (fr) 1995-03-02 1998-01-07 R.P. Scherer Limited Compositions pharmaceutiques comportant des inhibiteurs de monoamine-oxydase b
US6126968A (en) 1995-09-20 2000-10-03 Teva Pharmaceutical Industries, Ltd. Stable compositions containing N-propargyl-1-aminoindan
EP1892233A1 (fr) 2006-08-18 2008-02-27 Ratiopharm GmbH De nouveaux sels de la substance active rasagiline
US20100137447A1 (en) * 2007-04-30 2010-06-03 Ratiopharm Gmbh Method for the production of adsorbates of a rasagiline salt having a water-soluble adjuvant
EP2218444A2 (fr) * 2009-01-23 2010-08-18 Teva Pharmaceutical Industries, Ltd. Formulation de rasagiline à libération retardée
WO2010111264A2 (fr) 2009-03-24 2010-09-30 Dr. Reddy's Laboratories Ltd. Préparations de rasagiline
WO2011010324A1 (fr) 2009-07-23 2011-01-27 Alkem Laboratories Ltd. Compositions pharmaceutiques orales stables comprenant de la rasagiline et procédé
EP2389927A1 (fr) * 2010-05-30 2011-11-30 Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi Formulations pharmaceutiques de rasagiline

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
R. L. DOBSON, J. PACKAGING TECHNOL., 1987, pages 127 - 131

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115400090A (zh) * 2022-10-09 2022-11-29 北京新领先医药科技发展有限公司 一种雷沙吉兰的口崩片组合物及其制备方法

Similar Documents

Publication Publication Date Title
JP6764959B2 (ja) 医薬組成物
JP6574417B2 (ja) 非晶質ダパグリフロジンを含有する製剤
ES2389889T3 (es) Formulación de rasagilina de liberación retardada
KR101445757B1 (ko) 옥시코돈을 포함하는 과립 및 경구 붕해 정제
EP2902384A1 (fr) Formes de chlorhydrate d'ivabradine
EP2146693A2 (fr) Compositions à base de solifénacine
WO2014177491A1 (fr) Nouvelle forme solide de bromhydrate de 1-(2-((2,4-diméthylphényl)thio)phényl)pipérazine
WO2012131005A1 (fr) Composition pharmaceutique de sitagliptine
JP2018076372A (ja) アナグリプチン含有固形製剤
JP2024033014A (ja) 医薬組成物
BRPI0914164B1 (pt) Comistura para produção de comprimidos de desintegração rápida em um processo de formação de comprimido direto, seus usos, e formulações de comprimido
SG190406A1 (en) Formulations comprising methylthioninium chloride
EP3290037A1 (fr) Composition pharmaceutique pour administration par voie orale
WO2013175493A1 (fr) Compositions pharmaceutiques orales stables
KR20180122282A (ko) 수용해도 및 생체이용율이 개선된 조성물
EP3257499A1 (fr) Procédé pour la préparation de capsules de méthanesulfonate d'imatinib
CA2974375A1 (fr) Forme galenique solide stable de fingolimod
WO2014192022A1 (fr) Compositions pharmaceutiques de rasagiline
KR20240093577A (ko) 약학적 조성물
EP2996681B1 (fr) Composition pharmaceutique contenant du fingolimod
AU2013203333A1 (en) Pharmaceutical compositions
CN118119380A (zh) 药物组合物
WO2011139250A2 (fr) Formulation hydrodispersable

Legal Events

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

Ref document number: 13753353

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13753353

Country of ref document: EP

Kind code of ref document: A1