WO2006136927A1 - Preparation a liberation prolongee comprenant de la venlafaxine - Google Patents

Preparation a liberation prolongee comprenant de la venlafaxine Download PDF

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Publication number
WO2006136927A1
WO2006136927A1 PCT/IB2006/001690 IB2006001690W WO2006136927A1 WO 2006136927 A1 WO2006136927 A1 WO 2006136927A1 IB 2006001690 W IB2006001690 W IB 2006001690W WO 2006136927 A1 WO2006136927 A1 WO 2006136927A1
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WO
WIPO (PCT)
Prior art keywords
extended release
mini
pharmaceutical composition
venlafaxine
tablet
Prior art date
Application number
PCT/IB2006/001690
Other languages
English (en)
Inventor
Anandi Krishnan
Atul Patil
Amrinder Singh Rai
Muthaiyyan Esakki Kannan
Nilendu Sen
Suma P. Nair
Jagadish Pati
Original Assignee
Glenmark Pharmaceuticals 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 Glenmark Pharmaceuticals Limited filed Critical Glenmark Pharmaceuticals Limited
Publication of WO2006136927A1 publication Critical patent/WO2006136927A1/fr

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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
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates generally to extended release pharmaceutical formulations containing venlafaxine or a pharmaceutically acceptable salt thereof.
  • the active ingredient is conventionally compounded with cellulose ethers such as methyl cellulose, ethyl cellulose or hydroxypropylmethylcellulose with or without other excipients and the resulting mixture is pressed into tablets.
  • cellulose ethers such as methyl cellulose, ethyl cellulose or hydroxypropylmethylcellulose with or without other excipients
  • the cellulose ethers in the tablets swell upon hydration from moisture in the digestive system, thereby limiting exposure of the active ingredient to moisture.
  • the active ingredient As the cellulose ethers are gradually leached away by moisture, water more deeply penetrates the gel matrix and the active ingredient slowly dissolves and diffuses through the gel, making it available for absorption by the body.
  • extended release capsule dosage forms may be formulated by mixing the drug with one or more binding agents to form a uniform mixture which is then moistened with water or a solvent such as ethanol to form an extrudable plastic mass from which small diameter, e.g., 1 mm, cylinders of drug/matrix are extruded, broken into appropriate lengths and transformed into spheroids using spheronization equipment.
  • the spheroids after drying, may then be film-coated to retard dissolution.
  • the film-coated spheroids may then be placed in pharmaceutically acceptable capsules, such as starch or gelatin capsules, in the quantity needed to obtain the desired therapeutic effect.
  • spheroids are difficult and expensive to manufacture, particularly on a commercial scale.
  • U.S. Patent No. 6,274,171 and related EP 0797991 disclose encapsulated extended release formulations of venlafaxine hydrochloride which provide a once daily, encapsulated extended release dosage form with a flattened drug plasma profile and reduced side effects.
  • the encapsulated dosage form includes spheroids of venlafaxine hydrochloride, microcrystalline cellulose, and hydroxypropylmethylcellulose (HPMC), which are coated with a mixture of ethyl cellulose and HPMC.
  • HPMC hydroxypropylmethylcellulose
  • WO 99/22724 discloses encapsulated extended release formulations of venlafaxine hydrochloride.
  • the encapsulated dosage form includes spheroids of venlafaxine hydrochloride and microcrystalline cellulose wherein the spheroid is substantially free of HPMC and are coated with a mixture of ethyl cellulose and HPMC. As mentioned above, spheroids are difficult and expensive to manufacture on a commercial scale.
  • EP 1502587 Al discloses sustained release formulations of venlafaxine
  • HCl which contain functional cores of mini-tablets with or without a functional coating layer or film over the mini-tablets filled into a capsule so that the initial rapid release of venlafaxine HCl is limited.
  • the core of the contains venlafaxine HCl, a gelling agent, a non-swelling agent and a conjugation agent that forms bonds between the gelling agent and the non-swelling agent or between the drug substance and the gelling or the non- swelling agent, causing the swelling property of the core to be limited.
  • EP 1502587 further discloses that by suppressing the core and swellable gelling agents, the penetration of water through the core causing the diffusion of the drug substance and its rapid release to be limited during the initial steps of the wetting of the core thereby restricting the "burst" phenomenon.
  • the core has a major role in retarding the drug release of this formulation.
  • an extended release pharmaceutical composition in solid dosage form comprising one or more mini-tablets, each mini-tablet comprising a therapeutically effective amount of venlafaxine or a pharmaceutically acceptable salt thereof and an extended release coating associated with the mini-tablet, wherein the mini-tablet provides an immediate release of the venlafaxine or a pharmaceutically acceptable salt thereof and the extended release coating provides an extended release of the venlafaxine or pharmaceutically acceptable salt thereof.
  • an extended release formulation of venlafaxine or a pharmaceutically acceptable salt thereof in the form of mini-tablets filled in a capsule comprising a therapeutically effective amount of venlafaxine or a pharmaceutically acceptable salt thereof and an extended release coating associated with the mini-tablet, the extended release coating comprising a hydrophobic polymer, wherein the mini-tablet provides an immediate release of the venlafaxine or a pharmaceutically acceptable salt thereof and the extended release coating provides an extended release of the venlafaxine or pharmaceutically acceptable salt thereof.
  • an extended release formulation of venlafaxine or a pharmaceutically acceptable salt thereof in the form of mini-tablets having an extended release coating associated therewith and filled in a capsule comprising a therapeutically effective amount of venlafaxine hydrochloride, ethyl cellulose and microcrystalline cellulose; and the extended release coating comprising ethyl cellulose, a channel forming agent selected from the group of hydroxypropyl methylcellulose and polyvinyl pyrrolidone and a solvent selected from the group consisting of isopropyl alcohol, water, methylene chloride and mixtures thereof wherein the mini tablet provides an immediate release of the venlafaxine or a pharmaceutically acceptable salt thereof and the extended release coating provides an extended release of the venlafaxine or pharmaceutically acceptable salt thereof.
  • an extended release formulation of venlafaxine or a pharmaceutically acceptable salt thereof in the form of mini-tablets having an extended release coating associated therewith and filled in a capsule comprising about 40% to about 90% venlafaxine or a pharmaceutically acceptable salt thereof on a weight/weight (w/w) basis, about 5% w/w to about 50% w/w ethyl cellulose and about 10% w/w to about 50% w/w microcrystalline cellulose; and the extended release coating comprising about 1% w/w to about 10% w/w ethyl cellulose, about 0.1% w/w to about 5% w/w channel forming agent and a solvent, wherein the mini-tablet provides an immediate release of the venlafaxine or a pharmaceutically acceptable salt thereof and the extended release coating provides an extended release of the venlafaxine or pharmaceutically acceptable salt thereof.
  • a process for preparing an extended release formulation of venlafaxine or a pharmaceutically acceptable salt thereof comprising (a) blending a therapeutically effective amount of the venlafaxine or pharmaceutically acceptable salt thereof and diluent; (b) granulating the blended mixture with an aqueous or non-aqueous solution of binder and drying it; (c) lubricating the dried granules and compressing into mini tablets; (d) coating the mini-tablets with an aqueous or non-aqueous dispersion of a hydrophilic polymer- containing component; and (e) filling the coated mini-tablets obtained in step (d) into a capsule.
  • the extended release formulations of venlafaxine or a pharmaceutically acceptable salt thereof of the present invention are advantageously in the form of mini- tablets obtained in a simple and economical process.
  • the extended release formulations also provide a once daily dosage form and release the active ingredient in a predetermined manner over a period of at least 24 hours. Additionally it is believed that the extended release formulation of the present invention can be a bioequivalent to Effexor ® XR.
  • the term "therapeutically effective amount” as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment.
  • the “therapeutically effective amount” will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated.
  • the present invention relates to extended release solid dosage formulations containing at least the active pharmaceutical ingredient venlafaxine or a pharmaceutically acceptable salt thereof, e.g., venlafaxine HCl, as the active pharmaceutical ingredient.
  • the extended release solid dosage formulations include one or more mini-tablets containing at least venlafaxine or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients such that the mini-tablet(s) provides immediate release of the active pharmaceutical ingredient.
  • the mini-tablet also has an extended release coating associated therewith which provides an extended release of the venlafaxine or pharmaceutically acceptable salt thereof.
  • the extended release pharmaceutical formulation is in a once daily dosage form such that a therapeutically effective amount of the active ingredient can be released over a period of at least 24 hours.
  • the extended release coating degrades so that about 55 to about 90% of the venlafaxine or pharmaceutically acceptable salt thereof is released after about 12 hours as determined using USP Apparatus 1 at 100 rpm in water at 37°C.
  • the mini- tablets are advantageously filled into a capsule.
  • the mini-tablets can be prepared in any manner, such as by utilizing any conventional manufacturing technique, e.g., compression of non-spheroidal particles.
  • the mini-tablets can be produced by combining and/or granulating the active pharmaceutical ingredient and one or more pharmaceutically acceptable excipients in one or more procedures utilizing any appropriate techniques, such as by granulating in a low shear granulator, fluidized bed granulation, high shear granulator.
  • the mini-tablet can be in the size range of about 4 mm to about 8 mm.
  • the mini-tablet can be in the size range of about 4 mm to about 7 mm.
  • the mini-tablet can be in the size range of about 5 mm to about 6 mm.
  • the mini-tablet can be in the size range of about 5 mm.
  • the venlafaxine or pharmaceutically acceptable salt thereof will ordinarily be present in the mini-tablets in an amount ranging from about 40% w/w to about 90% w/w, preferably from about 45% w/w to about 75% w/w, and more preferably from about 45% w/w to about 60% w/w. Further, venlafaxine hydrochloride may be present in an amount from about 25 mg to about 35 mg per capsule.
  • Suitable excipients for use in forming the mini-tablet include, but are not limited to, diluents, hydrophobic polymers, glidants, lubricants, binders and the like and mixtures thereof.
  • Useful diluents include, but are not limited to, lactose, mannitol, microcrystalline cellulose, dicalcium phosphate and the like and mixtures thereof.
  • Useful hydrophobic polymers can be water-insoluble polymer and include, by way of example, ethylcellulose, ammonio methacrylate copolymers types A and B as described in USP, methacrylic acid copolymer types A, B and C as described in USP, polyacrylate dispersion 30% as described in Ph.Eur., polyvinyl acetate dispersion, cellulose acetate, cellulose propionate (low, medium or high molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate), poly(isobutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl
  • the viscosity of ethyl cellulose is typically measured at 25°C using 5% w/v ethylcellulose dissolved in a solvent blend of 80% toluene: 20% ethanol (w/w).
  • Different grades of ethylcellulose are ethocel std 4 premium, ethocel std 7FP premium, ethocel std 7 premium, ethocel std IOFP premium, ethocel std 1OP premium, ethocel std 2OP premium, ethocel std 45P premium, ethocel std IOOFP premium, ethocel IOOP having viscosity range of 3-5.5 cP, 6-8 cP, 6-8 cP, 9-11 cP, 9-11 cP, 18-22 cP, 41-49 cP, 90-110 cP, 90-110 cP respectively.
  • Ethylcellulose is prepared by treating purified cellulose with an alkaline solution, followed by ethylation of the alkali cellulose with chloroethane.
  • the ethylcellulose for use herein is an aqueous or non-aqueous dispersion of ethylcellulose.
  • the ethylcellulose for use herein is ethylcellulose 100 cP (e.g., Ethocel 100 cP Std. Prem. FP*).
  • Useful glidants include, but are not limited to, silicon dioxide, magnesium lauryl sulfate, magnesium oxide and the like can be added to the formulation to reduce interparticulate friction and to eliminate the problem associated with the flow of materials from larger to smaller apertures in the manufacturing presses.
  • Useful lubricants include, but are not limited to, magnesium stearate, stearic acid ,polyethylene glycol, glyceryl behenate, calcium stearate, glyceryl monostearate and the like and mixtures thereof.
  • the coating composition for providing an extended release of venlafaxine or pharmaceutically acceptable salt thereof can include hydrophobic polymers, channel forming agents, plasticizers, anti-tacking agents, fillers, coloring agents, opacifiers and the like and mixtures thereof.
  • the hydrophobic polymers are water-insoluble and include, but are not limited to, ethylcellulose, ammonio methacrylate copolymers types A and B as described in USP, methacrylic acid copolymer types A, B and C as described in USP, polyacrylate dispersion 30% as described in Ph.Eur., polyvinyl acetate dispersion, cellulose acetate, cellulose propionate (low, medium or high molecular weight), cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, poly(methyl methacrylate), poly(ethyl methacrylate), poly(butyl methacrylate), poly(isobutyl methacrylate), poly(hexyl methacrylate), poly(isodecyl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate),
  • a preferred hydrophobic polymer is an aqueous dispersion of ethylcellulose, e.g. Surelease ® , or ethylcellulose 22 cP (Ethyl Cellulose N-22 Pharm. ® ).
  • Suitable channel-forming agents include, but are not limited to, water soluble agents such as, for example, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, hydroxypropyl cellulose, sucrose, mannitol, lactose and the like and mixtures thereof.
  • a preferred channel-forming agents is hydroxypropyl methylcellulose and polyvinyl pyrrolidone.
  • Suitable plasticizers include propylene glycol, diethyl phthalate, triacetin, glycerin and the like and mixtures thereof.
  • the coating composition further contains one or more solvents.
  • Suitable solvents for the extended release coating can comprise various solvents including, but not limited to, isopropyl alcohol (IPA), water, methylene chloride and mixtures thereof.
  • IPA isopropyl alcohol
  • methylene chloride a solvent that can be used such as isopropyl alcohol and water, isopropyl alcohol and methylene chloride and the like.
  • the mini-tablets can be coated with the extended release coating using various techniques, such as conventional coating techniques such as perforated pan, fluidized bed technique or spraying. These methods are commonly understood by individuals who are practicing the art tablet manufacture.
  • the angle of spray guns utilized in spayed on the coating can be varied, such as, but not limited to between about 30° and about 75°.
  • the coating composition can constitute about 1 to about 40 percent by weight of the formulation and preferably from about 5 to about 20 percent by weight of the formulation.
  • each mini -tablet can be given varying coats of the extended release coating, the material of the coating may be varied to achieve a controlled release coating, or a combination of varying coating thicknesses and coating materials may be used. As one skilled in the art will readily appreciate, some of the mini-tablets, e.g., less than about twenty five percent, may be left completely uncoated for immediate release. The mini- tablets may then be filled in a capsule to achieve a blend of mini-tablets with varying coatings.
  • the extended release formulations of the present invention may be produced in a uniform dosage for a specified dissolution profile upon oral administration by techniques understood in the art.
  • the mini-tablet components may be blended for uniformity with a desired concentration of active ingredient, then granulated and dried.
  • the resulting non-spheroidal granules can then be sifted through a mesh of appropriate pore size to obtain a batch of uniform and prescribed size of the granules which can then be formed into mini-tablets.
  • the resulting mini-tablets can be coated and resifted to remove any agglomerates produced in the coating steps. During the coating process samples of the coated mini-tablets may be tested for their distribution profile. If the dissolution occurs too rapidly, additional coating may be applied until the mini-tablets present a desired dissolution rate.
  • the pharmaceutical compositions of the present invention can be obtained by at least blending venlafaxine or a pharmaceutically acceptable salt thereof with a diluent/filler and a hydrophobic polymer followed by granulation in, for example, a high shear mixer, using an organic solvent in which both the drug substance and the hydrophobic polymer are soluble in order to form bridges between the drug substance and the hydrophobic polymer.
  • the granules are dried and reduced to the desired size, lubricated with one or more lubricant(s) and formed into mini-tablets.
  • the granulation equipment used can be a fluidized bed granulator in which venlafaxine or a pharmaceutically acceptable salt thereof, hydrophobic polymer and diluent are granulated by spraying the organic solvent.
  • the lubricated blend can then be compressed into mini-tablets and coated with the extended release coating composition.
  • the granulation process can be an aqueous process in which venlafaxine or a pharmaceutically acceptable salt thereof and a diluent are granulated with an aqueous dispersion of ethylcellulose (e.g. Surelease ® or Aquacoat ® ) or ammonio methacrylate copolymer (Eudragit RS 30D ® or Eudragit RL 30D ® ) and formed into mini-tablets.
  • the coating composition can also be an aqueous dispersion of ethylcellulose (e.g.
  • the preferable coating composition includes an ethylcellulose aqueous dispersion and hydroxypropyl methylcellulose.
  • the individual components employed in compositions of the present invention can be present in amounts as set forth in Table 1.
  • the mini-tablets prepared in Example 1 were coated with a coating composition set forth in Table 3.
  • the coating composition was applied over the mini- tablets at a coating level of 10.4% w/w.
  • the coated mini-tablets were filled into a pharmaceutically acceptable gelatin capsule conventionally to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 5.
  • the coating composition set forth in Table 3 was applied over the mini- tablets of Example 1 at a coating level of 12.5% w/w.
  • the mini-tablets were filled into a pharmaceutically acceptable gelatin capsule conventionally to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 5.
  • the mini-tablets prepared in Example 1 were coated with a coating composition set forth in Table 3.
  • the coating composition of Table 4 was applied over the coated mini-tablets at a coating level of 12.5% w/w.
  • the coated mini-tablets were filled into a pharmaceutically acceptable gelatin capsule to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 5.
  • Examples 2-4 were carried out.
  • the dissolution of the venlafaxine hydrochloride ER capsules was determined as directed in the U.S. Pharmacopoeia (USP) in 900 ml of dearated water at 37°C using an USP Dissolution Apparatus Type I at an agitation of 100 rotations per minute (rpm).
  • the uncoated mini-tablets of Example 1 were also analyzed for the dissolution rate which is exemplary of an immediate release profile.
  • the dissolution study of the Effexor ® XR Capsules 150 mg was studied under the same conditions. The results of the dissolution studies are set forth in Table 5.
  • the dissolved venlafaxine is expressed in cumulative percent of drug dissolved over an elapsed time period in minutes. TABLE 5
  • mini-tablets of the present invention provide a means to control the dissolution rate of venlafaxine by varying the thickness of the coating composition. Accordingly, the desired dissolution of the venlafaxine extended release capsules can be achieved with the pharmaceutical compositions of the present invention thus providing a simple means of achieving dose-proportionality between different strengths.
  • the mini-tablets prepared in Example 5 were coated with a coating composition set forth in Table 7.
  • the coating composition was applied over the mini- tablets at a coating level of 10.4% w/w.
  • the coated mini-tablets were filled into a pharmaceutically acceptable gelatin capsule to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 10.
  • the coating composition set forth in Table 7 was applied over the mini- tablets of Example 5 at a coating level of 12.5% w/w.
  • the coated mini-tablets were filled into a pharmaceutically acceptable gelatin capsule conventionally to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 10.
  • the mini-tablets of this example were coated with a coating composition set forth in Table 9.
  • the coating composition of Table 9 was applied over the mini-tablets at a coating level of 15% w/w.
  • the coated mini-tablets were filled into a pharmaceutically acceptable gelatin capsule to provide a 360 mg capsule.
  • the dissolution profile for the capsule containing the coated mini-tablets of this example is set forth in Table 10.
  • Examples 6-8 were carried out.
  • the dissolution of the venlafaxine hydrochloride ER capsules was determined as directed in the U.S. Pharmacopoeia (USP) in 900 ml of dearated water at 37 0 C using an USP Dissolution Apparatus Type I at an agitation of 100 rotations per minute (rpm).
  • the uncoated mini-tablets of Example 5 were also analyzed for the dissolution rate which is exemplary of an immediate release profile.
  • the dissolution study of the Effexor ® XR Capsules 150 mg was studied under the same conditions. The results of the dissolution studies are set forth in Table 10.
  • the dissolved venlafaxine is expressed in cumulative percent of drug dissolved over an elapsed time period in minutes.
  • mini-tablets of the present invention provide a means to control the dissolution rate of venlafaxine by varying the thickness of the coating composition. Accordingly, the desired dissolution of the venlafaxine extended release capsules can be achieved with the pharmaceutical compositions of the present invention thus providing a simple means of achieving dose-proportionality between different strengths.
  • Examples 1-8 are as follows.
  • Venlafaxine hydrochloride was blended with Ethocel 100 cP Std. Prem. FP and Avicel PH 101 in a high shear mixer.
  • the blended mass was granulated in the mixer using absolute ethanol.
  • the blended granules were lubricated with magnesium stearate.
  • the lubricated granules were compressed into mini-tablets of 3 mm diameter.
  • the mini-tablets were coated at varying thicknesses using a perforated coating pan with the coating compositions set forth in Tables 3, 4, 7 and 9.

Abstract

La présente invention concerne une composition pharmaceutique à libération prolongée sous forme de dosage solide comprenant un ou plusieurs mini-cachets, lesquels comprennent une quantité thérapeutiquement efficace de venlafaxine ou d'un sel de ce composé répondant aux normes pharmaceutiques et un film de libération lente associé à celui-ci, ces mini-cachets fournissant une libération immédiate de venlafaxine ou du sel de ce composé répondant aux normes pharmaceutiques et ce film de libération lente permettant une libération lente de la venlafaxine ou des sels de ce composé répondant aux normes pharmaceutiques.
PCT/IB2006/001690 2005-06-22 2006-06-21 Preparation a liberation prolongee comprenant de la venlafaxine WO2006136927A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN739MU2005 2005-06-22
IN739/MUM/2005 2005-06-22
US72771805P 2005-10-18 2005-10-18
US60/727,718 2005-10-18

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6274171B1 (en) * 1996-03-25 2001-08-14 American Home Products Corporation Extended release formulation of venlafaxine hydrochloride
US20030190353A1 (en) * 2002-03-28 2003-10-09 Synthon Bv Low water-soluble venlafaxine salts
EP1473030A1 (fr) * 2003-05-02 2004-11-03 Dexcel Ltd. Formulation de comprimé à libération prolongée du venlafaxine
EP1502587A1 (fr) * 2003-07-30 2005-02-02 Pharmathen S.A. Formulation à libération prolongée du chlorhydrate de Venlafaxine
US20050169985A1 (en) * 2004-02-04 2005-08-04 Sampad Bhattacharya Extended release formulation of venlafaxine hydrochloride
US20050226923A1 (en) * 2004-04-07 2005-10-13 Gassert Chad M Venlafaxine compositions in the form of microtablets
WO2005112901A1 (fr) * 2004-05-21 2005-12-01 Lupin Ltd. Nouvelle composition a liberation etendue de chlorhydrate de venlafaxine contenant de l'acetate de polyvinyle

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6274171B1 (en) * 1996-03-25 2001-08-14 American Home Products Corporation Extended release formulation of venlafaxine hydrochloride
US20030190353A1 (en) * 2002-03-28 2003-10-09 Synthon Bv Low water-soluble venlafaxine salts
WO2003082805A1 (fr) * 2002-03-28 2003-10-09 Synthon B.V. Sels de venlafaxine faiblement solubles dans l'eau
EP1473030A1 (fr) * 2003-05-02 2004-11-03 Dexcel Ltd. Formulation de comprimé à libération prolongée du venlafaxine
EP1502587A1 (fr) * 2003-07-30 2005-02-02 Pharmathen S.A. Formulation à libération prolongée du chlorhydrate de Venlafaxine
US20050169985A1 (en) * 2004-02-04 2005-08-04 Sampad Bhattacharya Extended release formulation of venlafaxine hydrochloride
US20050226923A1 (en) * 2004-04-07 2005-10-13 Gassert Chad M Venlafaxine compositions in the form of microtablets
WO2005112901A1 (fr) * 2004-05-21 2005-12-01 Lupin Ltd. Nouvelle composition a liberation etendue de chlorhydrate de venlafaxine contenant de l'acetate de polyvinyle

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