WO2009026621A1 - Composé et composition pharmaceutiques - Google Patents

Composé et composition pharmaceutiques Download PDF

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Publication number
WO2009026621A1
WO2009026621A1 PCT/AU2008/001249 AU2008001249W WO2009026621A1 WO 2009026621 A1 WO2009026621 A1 WO 2009026621A1 AU 2008001249 W AU2008001249 W AU 2008001249W WO 2009026621 A1 WO2009026621 A1 WO 2009026621A1
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WO
WIPO (PCT)
Prior art keywords
paliperidone
particle size
pharmaceutically acceptable
particulate
acceptable salt
Prior art date
Application number
PCT/AU2008/001249
Other languages
English (en)
Inventor
Brett Antony Mooney
Panagiotas Keramidas
Original Assignee
Alphapharm Pty Ltd
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
Priority claimed from AU2007904647A external-priority patent/AU2007904647A0/en
Application filed by Alphapharm Pty Ltd filed Critical Alphapharm Pty Ltd
Publication of WO2009026621A1 publication Critical patent/WO2009026621A1/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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—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
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—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
    • A61K9/20—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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to pharmaceutical compound comprising paliperidone exhibiting a particular particle size and compositions comprising Vietnamese paliperidone , as the active ingredient. Further, the invention relates to the use of such compositions in the manufacture of medicaments for the treatment of conditions for which paliperidone is effective and processes to manufacture these compositions.
  • Paliperidone is indicated for the acute and maintenance treatment of schizophrenia.
  • U.S. Patent 5,254,556 (assigned to Janssen Pharmaceutics, N.V.) discloses alkanoic acid esters of paliperidone.
  • U.S. Patent 6,320,048 (assigned to Janssen Pharmaceutica, N,V.) discloses a process to manufacture the enantiomeric forms of paliperidone,
  • U.S. Patent S, 077, 843 (assigned to Janssen Pharmaceutica, N-V.) discloses paliperidone fatty acid esters or salts, such as palmitate.
  • U.S. Patent 6,555,544 (assigned to Janssen Pharmaceutica, N.V.) discloses a paliperidone having a submicron particle size suitable for administration via injection as an aqueous suspension.
  • U.S. Patent Applications 2004/0092534, 2005/ 0208132, 2005/0232995 & 2006/0189635 (assigned to Alza Corp.) disclose a paliperidone containing dosage form and methods for treating a condition responsive to paliperidone using such dosage form wherein the dosage form releases the paliperidone at a substantially ascending release rate for a prolonged period of time.
  • Patent Application 2006/0034927 discloses a sustained-release dosage form exhibiting a biphasic release profile wherein one layer contains microencapsulated drug and an adjacent layer contains non- microencapsulated drug.
  • WO 2006/085856 discloses a sustained-release formulation of atypical antipsychotic drug that exhibits a defined rate of release .
  • Paliperidone is approved for marketing in the US under the tradename Invega and is an extended-release oral tablet in 3mg, 6mg, 9mg and 12mg strengths of the paliperidone free base.
  • the dosage form of this product utilises a semi-permeable membrane with a hole through it and an osmotic pump system to facilitate the migration of the paliperidone out of the tablet.
  • This type of extended- release system is generally referred to as an OROS* system by Alza Corporation.
  • An aspect of pharmaceutical formulation that affects the rate of delivery or the bioavailability of the pharmaceutically active substance is particle size.
  • particle size reduction fails to increase absorption rate.
  • dissolution is not the rate limiting step.
  • raicronisation can sometimes increase the tendency of the particles to aggregate which may lead to a decrease in surface area.
  • extremely small sizes may be inadvisable for some drug substances as adsorbed air or crystal growth might act as dissolution rate limiting steps .
  • the micronisation process itself can also lead to degradation of the active ingredient.
  • relatively larger particle sizes of drugs that have low aqueous solubility can suffer from the problem of poor dissolution and consequently poor bioavailability.
  • compositions of paliperidone to provide improved or effective compositions that keep the beneficial properties of micronised particles, such as an increase in aqueous solubility, leading to an increase in bioavailability whilst overcoming the above highlighted problems of the prior art .
  • the inventors have surprisingly found that paliperidone of a defined particle size affords suitable properties .
  • a particulate paliperidone, or a pharmaceutically acceptable salt thereof having a D 50 particle size of between about l ⁇ m and about 40 ⁇ m.
  • the D 50 particle size diameter is approximately 2-30 ⁇ m.
  • D 50 particle size diameter is approximately 2-20 ⁇ m.
  • Particulate paliperidone may be used to prepare pharmaceutical compositions further comprising a pharmaceutically acceptable excipient.
  • a pharmaceutical composition comprising paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m and further comprising one or more pharmaceutically acceptable excipients .
  • composition is a tablet composition. In an embodiment the tablet is coated. In an alternative embodiment the composition is a capsule.
  • composition comprises paliperidone in an amount of approximately 1-90% by weight of the composition.
  • composition further comprises wetting agents/surfactants.
  • the wetting agent is Tween (polysorbate) or sodium lauryl sulphate.
  • the pharmaceutical composition can optionally include one or more additional API's.
  • the API's are selected from the group comprising anti-depressants, ACE inhibitors, nicotinic receptor agonists or antagonists or glycine transporter type (GIyT-I) inhibitors.
  • a paliperidone or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m in the manufacture of a medicament for the acute or maintenance treatment of schizophrenia, treatment of sleep disorders, treatment of substance abuse or treatment of a mental disorder in a psychiatric patient with reduced hepatic function.
  • a method for the acute or maintenance treatment of schizophrenia, treatment of sleep disorders, substance abuse or a mental disorder in a psychiatric patient with reduced hepatic function by administering a particulate paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m.
  • a method for the acute or maintenance treatment of schizophrenia, treatment of sleep disorders, substance abuse or a mental disorder in a psychiatric patient with reduced hepatic function by administering a composition comprising a particulate paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m and at least one pharmaceutically acceptable excipient.
  • a process of preparing a pharmaceutical composition comprising paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m comprising admixing said paliperidone with one or more pharmaceutically acceptable carriers.
  • the composition is prepared by a process comprising wet or dry granulation techniques.
  • a particularly preferred process comprises : i) admixing the particulate paliperidone with one or more pharmaceutical excipients; ii) forming a wet granulation mixture; iii) granulating said wet granulation mixture; iv) drying the granules,- v) compressing the granules into tablet form; and vi) optionally coating the tablet composition.
  • a still further aspect provides a process for preparing particulate paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size of between about 1 ⁇ m and about 40 ⁇ m comprising subjecting paliperidone, or a pharmaceutically acceptable salt thereof, to a technique chosen from the list comprising conventional comminution and de-agglomeration, micro- fluidisation, high pressure homogenisation and chemical treatment .
  • the comminution techniques comprise grinding or milling in an air-jet mill or impact mill, a ball mill, vibration mill, mortar mill or pin mill.
  • the chemical treatment comprises controlled precipitation or recrystallisation.
  • compositions and paliperidone as disclosed herein lend themselves to a number of formulation types.
  • controlled release compositions are within the scope of the invention.
  • Such controlled-release compositions may comprise extended-release, sustained-release, delayed-release or modified-release.
  • Further embodiments may also comprise multi-phasic release compositions wherein a proportion of the paliperidone is released immediately and release of the remainder is delayed.
  • the composition may comprise additional API's with differing release kinetics.
  • a pharmaceutical composition comprising paliperidone, or a pharmaceutically acceptable salt thereof, having a D 50 particle size diameter of between 1 and 40 ⁇ m.
  • conventional comminution and de ⁇ agglomeration techniques may be used, for example grinding in an air-jet mill or impact mill, a ball mill, vibration mill, mortar mill or pin mill. Further techniques such as micro-fluidisation can also be used. Chemical techniques such as controlled precipitation/ recrystallisation may also be employed.
  • the known particle size analysis methods are suitable for determining the median particle size, for example particle size measurement using light, for example light- scattering methods or turbidimetric methods, sedimentation methods, for example pipette analysis using an Andreassen pipette, sedimentation scales, photosedimentometers or sedimentation in a centrifugal force field, pulse methods, for example using a Coulter counter, or sorting by means of gravitational or centrifugal force.
  • Those methods are described, inter alia, in Voigt, loc . cit., pages 64-79.
  • the composition may contain pharmaceutically acceptable excipients commonly used in pharmaceutical compositions, e.g. for oral administration.
  • the composition may be in the form of a tablet which comprises, a) a tablet core comprising a therapeutically effective dose of the paliperidone having a D 50 particle size of approximately from 1 to 40 ⁇ m and further excipients that are suitable for the manufacture of the compositions according to the invention.
  • the palperidone is in finely ground form.
  • the D 50 particle size is 2 to 30 ⁇ m. In an embodiment the D 50 particle size is 2 to 20 ⁇ m.
  • the composition comprises a tablet composition.
  • Such tablets comprise paliperidone of fine particle size and as such may be formulated into dosage forms, e.g. solid oral dosage forms such as the preferred tablets with relative ease.
  • the fine particle size may also be beneficial in improving the bioavailability of paliperidone.
  • the compositions meet all customary requirements, such as storage stability and colour stability.
  • Tablets according to the invention may be manufactured by any means at the disposal of the skilled practitioner. Commonly used means include compressing paliperidone with conventional tabletting excipients to form a tablet core using conventional tabletting processes. Optionally the tablet cores may be coated. Coatings may comprise one or more of modified release coatings, coatings that effect the release kinetics of paliperidone and conventional immediate release coatings for example the Opadry series of aqueous film-coatings systems manufactured by Colorcon.
  • the tablet cores may be produced using conventional methods known in the art for example granulation methods, such as wet or dry granulation, with optional comminution of the granules and with subsequent compression and coating. Granulation methods are described, for example, in Voigt, loc. cit., pages 156-169.
  • Suitable excipients for the production of granules are, for example pulverulent fillers optionally having flow-conditioning properties, for example talcum, silicon dioxide, for example synthetic amorphous anhydrous silica acid of the Syloid ® X type (Grace) , for example SYLOID ⁇ 244
  • microcrystalline cellulose for example the Avicel types (FMC Corp.) such as AVICEL ® PHlOl, 102, 105, RC581 or RC 591, Emcocel ® type (Mendell Corp.) or Elcema type
  • carbohydrates such as sugars, sugar alcohols, starches or starch derivatives, for example saccharose, lactose, dextrose, glucose, sorbitol, mannitol, xylitol, potato starch, maize starch, rice starch, wheat starch or amylopectin, tricalcium phosphate, calcium hydrogen phosphate or magnesium trisilicate,- particularly preferred is microcrystalline cellulose; binders, such as gelatin, tragacanth, agar, alginic acid, cellulose ethers, for example methylcellulose, carboxymethylcellulose or hydroxypropyl methylcellulose, polyethylene glycols or ethylene oxide homopolymers , especially having a degree of polymerisation of approximately from 2.O x 10 3 to 1.0 x 10 s and an approximate molecular weight of about from 1.0 x 10 5 to 5.0 x 10 6 , for example excipients known by the name Polyoxe ® (Union Carbide
  • Granules may be produced in a manner known per se, for example using wet granulation methods known for the production of "built-up" granules or "broken-down" granules .
  • Methods for the formation of built-up granules may operate continuously and comprise, for example simul- taneously spraying the granulation mass with granulation solution and drying, for example in a drum granulator, in pan granulators, on disc granulators, in a fluidised bed, by spray-drying or spray-solidifying, or operate dis- c ⁇ ntinuously, for example in a fluidised bed, in a batch mixer or in a spray-drying drum.
  • methods for the production of broken-down granules may be employed. These methods may be carried out discontinuously whereby the granulation mass first forms a wet aggregate with the granulation solution, which aggregate is then comminuted or formed into granules of the desired particle size and the granules then being dried.
  • Suitable equipment for the granulation step are planetary mixers, low and high shear mixers, wet granulation equipment including extruders and spheronisers include, for example, apparatus from the companies Corporation Corporation, Glatt, Diosna, Fielder, Collette, Alexanderwerk, Ytron, Werner & Pfleiderer, Fuji, Nica, Caleva and Gabler .
  • the granulation mass consists of comminuted, preferably ground, paliperidone and the excipients mentioned above, for example pulverulent fillers, such as microcrystalline cellulose of the AVICEL ® type.
  • AVICEL ® PH 102 is especially suitable, or wetting agents/surfactants.
  • Sodium lauryl sulphate or alternatively Tween ® (poly- sorbate) are particularly preferred surfactants.
  • the granulation mass may be in the form of a premix or may be obtained by mixing the paliperidone into one or more excipients or mixing the excipients into the paliperidone.
  • the wet granules are preferably dried, for example in the described manner by tray drying in an oven or drying in a fluidised bed dryer.
  • tablet cores are produced using the so-called compacting or dry granulation method in which the active ingredient is compressed with the excipients to form relatively large mouldings, for example slugs or ribbons, which are comminuted by grinding, and the ground material is compressed to form tablet cores.
  • the granules are made by fluid bed granulation techniques either by spraying drug containing liquid onto small carrier particles or by forming the particles from the liquid and building upon them in subsequent passes through the fluid bed apparatus.
  • Suitable excipients for the compacting method are preferably those which are suitable for the conventional direct compression methods, for example dry binders, such as starches, for example potato, wheat and maize starch, microcrystalline cellulose, for example commercial products available under the trademarks Avicel *8 , FiltrakTM, Hewetene or Pharmacel , highly dispersed silicon dioxide, for example Aerosil ® , mannitol, lactose, and also polyethylene glycol, especially having a molecular weight of from 4000 to 6000, cross-linked polyvinylpyrrolidone (Polyplasdones XL or Kollidone CL) , cross-linked carboxy- methylcellulose (Acdisol 0 X CMC-XL) , carboxymethylcellulose
  • dry binders such as starches, for example potato, wheat and maize starch, microcrystalline cellulose, for example commercial products available under the trademarks Avicel *8 , FiltrakTM, Hewetene or Pharmacel , highly dispersed
  • Emcompress or talcum Emcompress or talcum.
  • lubricants such as magnesium stearate.
  • Compression to form tablet cores may be carried out in conventional tabletting machines, for example EK-O Korsch eccentric tabletting machines or rotary tabletting machines such as Courtoy, Killian and Manesty Unipress.
  • the tablet cores may be of various shapes, for example round, oval, oblong, cylindrical etc., and various sizes, depending on the amount of paliperidone .
  • Controlled-release systems such as extended-release and sustained-release can be achieved by incorporating the active substance into a polymer matrix whereby the polymer acts to impede and/or control the flow of moisture and/or dissolved active substance within the dosage form. Control of the release of the active substance is believed to be achieved by the polymer swelling and reducing the rate of the passage of fluid. The drug then dissolves and drug laden fluid migrates back through the polymer and/or the polymer slowly erodes to release the drug into the body. This dosage form erosion also acts to present new areas of polymer/drug mixture that has not previously been exposed to the environment (ie. gastrointestinal system and corresponding fluids, etc) .
  • Polymers suitable to act as release controlling agents in a matrix system include cellulosic polymers such as HPMC KlOOMCR, HPMC KlOO, HPMC phthalate, ethylcellulose, cellulose acetate phthalate; Eudragit ® polymers such as RL, RS, NM30D, NE30D, NE40D, FS30D; a mixture of polyvinylacetate and polyvinylalcohol such as Kollidon ⁇ SR (trademark by BASF) ; polyvinyl acetate phthalate; alginates such as propylene glycol alginate, sodium alginate, alginic acid; or any combination thereof.
  • a non-polymeric material that can be utilised to effect the rate of release of the active pharmaceutical substance in a matrix system, either solely or in combination with a polymeric material is hydrogenated vegetable oil.
  • a polymer system can be applied as a coating to compressed tablet cores or granules in order to provide a controlling layer thereon, either separately or in combination with a matrix control system.
  • Controlled- release coating systems include the use of water- impermeable polymer coatings having a hole through the coating layer in combination with an osmotic pump system such as the OROS ® technology (trademark by ALZA Corp) ; delayed-release or enteric coating systems such as cellulosic polymers such as hydroxypropyl methylcellulose (HPMC) lower viscosity grades, HPMC KlOOMCR, HPMC KlOO, HPMC acetyl succinate, HPMC phthalate, ethylcellulose, cellulose acetyl phthalate; Eudragit ® polymers such as RL, RS, NM30D, NE30D, NE40D, L100-55, L30D-55, FS30D; a mixture of polyvinylacetate and polyvinylalcohol
  • Any coating system may also require the use of a protective and/or separating subcoat(s) .
  • This can be achieved by applying a .layer of polyvinylacetate; polyvinylpyrrolidone based products such as povidone, copovidone,- a polyvinyl alcohol - polyethylene glycol graft polymer known as Kollidon ® IR (trademark by BASF) ; cellulosic coating systems such as HPMC, Opadry or Opadry II systems (trademark by Colorcon) ; talc; sugars such sucrose, dextrose, lactose and the like; or other inert pharmaceutically acceptable excipient (s) .
  • Example 1 The ingredients of the pharmaceutical composition according to the invention can be prepared in accordance with acceptable pharmaceutical manufacturing practices .
  • the manufacturing process will comprise wet granulation for example as described above, because of the amount of active pharmaceutical ingredient (API) required and also the lower compressibility of material at the preferred particle size.
  • API active pharmaceutical ingredient
  • An exemplary extended-release composition according to the invention is shown in Table 1.
  • a 9mg extended-release composition was prepared according to the following:
  • Example 2 A 9mg extended-release composition was prepared according to the following:
  • compositions can be modified as required for example by the inclusion of colorants or taste enhancers and/or the application of a coating.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Addiction (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne la palipéridone particulaire, ou un sel de celle-ci acceptable sur le plan pharmaceutique, présentant un diamètre médian de particules, D50, compris entre environ 1 et environ 40 µm.
PCT/AU2008/001249 2007-08-29 2008-08-25 Composé et composition pharmaceutiques WO2009026621A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2007904647A AU2007904647A0 (en) 2007-08-29 Pharmaceutical Compound and Composition
AU2007904647 2007-08-29

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WO2009026621A1 true WO2009026621A1 (fr) 2009-03-05

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009109993A1 (fr) * 2008-02-04 2009-09-11 Torrent Pharmaceuticals Ltd. Forme pharmaceutique à libération prolongée de palipéridone
WO2010009900A1 (fr) * 2008-07-25 2010-01-28 Krka, D.D. Novo Mesto Composition de palipéridone comprenant des particules de matrice solide
US9271939B2 (en) 2010-03-15 2016-03-01 Inventia Healthcare Private Limited Stabilized prolonged release pharmaceutical composition comprising atypical antipsychotic
CN106137985A (zh) * 2016-08-04 2016-11-23 齐鲁制药有限公司 一种稳定的棕榈酸帕利哌酮长效制剂
WO2021104460A1 (fr) * 2019-11-29 2021-06-03 江苏恩华药业股份有限公司 Procédé de préparation d'une suspension de palmitate de palipéridone

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5158952A (en) * 1988-11-07 1992-10-27 Janssen Pharmaceutica N.V. 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use
WO1999025354A2 (fr) * 1997-11-17 1999-05-27 Janssen Pharmaceutica N.V. Suspensions aqueuses d'esters d'acides gras de 9-hydroxy-risperidone de l'ordre du sous-micron
WO2005115346A2 (fr) * 2004-05-28 2005-12-08 Actavis Group Hf. Composition contenant de la risperidone
WO2006085856A1 (fr) * 2005-02-04 2006-08-17 Alza Corporation Procedes et formes pharmaceutiques destines a reduire les effets secondaires des derives de benzisozazole
WO2006114384A1 (fr) * 2005-04-25 2006-11-02 Janssen Pharmaceutica N.V. Preparation d'ester de 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4h-pyridio[1,2-a]pyrimidin-4-one palmitate aseptique

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5158952A (en) * 1988-11-07 1992-10-27 Janssen Pharmaceutica N.V. 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use
WO1999025354A2 (fr) * 1997-11-17 1999-05-27 Janssen Pharmaceutica N.V. Suspensions aqueuses d'esters d'acides gras de 9-hydroxy-risperidone de l'ordre du sous-micron
WO2005115346A2 (fr) * 2004-05-28 2005-12-08 Actavis Group Hf. Composition contenant de la risperidone
WO2006085856A1 (fr) * 2005-02-04 2006-08-17 Alza Corporation Procedes et formes pharmaceutiques destines a reduire les effets secondaires des derives de benzisozazole
WO2006114384A1 (fr) * 2005-04-25 2006-11-02 Janssen Pharmaceutica N.V. Preparation d'ester de 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4h-pyridio[1,2-a]pyrimidin-4-one palmitate aseptique

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009109993A1 (fr) * 2008-02-04 2009-09-11 Torrent Pharmaceuticals Ltd. Forme pharmaceutique à libération prolongée de palipéridone
WO2010009900A1 (fr) * 2008-07-25 2010-01-28 Krka, D.D. Novo Mesto Composition de palipéridone comprenant des particules de matrice solide
US9271939B2 (en) 2010-03-15 2016-03-01 Inventia Healthcare Private Limited Stabilized prolonged release pharmaceutical composition comprising atypical antipsychotic
CN106137985A (zh) * 2016-08-04 2016-11-23 齐鲁制药有限公司 一种稳定的棕榈酸帕利哌酮长效制剂
CN106137985B (zh) * 2016-08-04 2019-03-08 齐鲁制药有限公司 一种稳定的棕榈酸帕利哌酮长效制剂
WO2021104460A1 (fr) * 2019-11-29 2021-06-03 江苏恩华药业股份有限公司 Procédé de préparation d'une suspension de palmitate de palipéridone

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