WO2007011131A1 - Comprimes stables a liberation controlee contenant de la tolterodine - Google Patents

Comprimes stables a liberation controlee contenant de la tolterodine Download PDF

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Publication number
WO2007011131A1
WO2007011131A1 PCT/KR2006/002764 KR2006002764W WO2007011131A1 WO 2007011131 A1 WO2007011131 A1 WO 2007011131A1 KR 2006002764 W KR2006002764 W KR 2006002764W WO 2007011131 A1 WO2007011131 A1 WO 2007011131A1
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WO
WIPO (PCT)
Prior art keywords
release
drug
controlled
pellet
layer
Prior art date
Application number
PCT/KR2006/002764
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English (en)
Inventor
Hee-Jong Shin
Jong-Lae Lim
Koong-Kwon Nam
Original Assignee
Chong Kun Dang Pharmaceutical Corp.
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Filing date
Publication date
Application filed by Chong Kun Dang Pharmaceutical Corp. filed Critical Chong Kun Dang Pharmaceutical Corp.
Publication of WO2007011131A1 publication Critical patent/WO2007011131A1/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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core

Definitions

  • the present invention relates to a novel pharmaceutical composition which is capable of improving the stability over time of a drug pellet in the course of storage and distribution of the pellet controlling drug release. More specifically, the present invention relates to a novel pharmaceutical composition which is capable of preventing moisture-induced changes in a drug-release rate that may occur during storage and distribution of a drug pellet, by coating a controlled-release pellet, particularly sustained-release pellet, comprising tolterodine, a tolterodine compound or a pharmaceutically acceptable salt thereof as a drug of interest, with a dimethylaminoethyl methacrylate/methyl methacrylate copolymer (hereinafter, referred to as "Eudragit E”) or polyvinylacetal diethylaminoacetate (hereinafter, referred to as "AEA”) which is insoluble at a pH of 5.5 or higher.
  • Eudragit E dimethylaminoethyl methacrylate/methyl methacrylate copolymer
  • AEA polyvinylacetal die
  • Korean Patent Registration No. 10-0467384 discloses a controlled- release pellet composition
  • a controlled- release pellet composition comprising: (i) a core unit of a substantially water- soluble or water-swellable inert material; (ii) a first layer on the core unit of a substantially water-insoluble polymer; (iii) a second layer covering the first layer and containing an active ingredient; and (iv) a third layer of polymer on the second layer effective for controlled release of the active ingredient, wherein the first layer is adapted to control water penetration into the core.
  • the inventors of the present invention have discovered the problem that the drug-release rate exhibits severe variations depending upon a storage duration when the-thus prepared pellet of the above Korean Patent is stored under accelerated conditions
  • a controlled-release pellet composition comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material or wax; (ii) a first layer covering the core unit and containing an active ingredient; and (iii) a second layer of polymer on the first layer effective for controlled release of the active ingredient, i.e., without inclusion of a layer to control water penetration into the core.
  • Eudragit E or AEA it was possible to overcome the problems associated changes in the drug-release rate over time during storage and distribution of the drug pellet, while not causing significant changes in the drug-release rate due to such a coating.
  • sustained-release formulations hi particular, when drug formulations are developed in the form of a pellet, it is possible to minimize variability of the drug-release rate due to various in vivo factors such as gastrointestinal motility in individual patients, as compared to tablets in the form of a matrix. Therefore, it is known that pellet formulations are advantageous to reduce between- and within-patient variability in drug efficacy.
  • pellet formulations are advantageous to reduce between- and within-patient variability in drug efficacy.
  • a common type of pharmaceutical formulations other than a sustained-release type exhibits sufficient release of active ingredients within up to 4 hours, increases/decreases in the drug-release rate over time after preparation of the pharmaceutical formulations may have little effects on the treatment of patients and expression of drug-induced toxicity.
  • a single dose thereof is 1.5 to 3-fold higher than that of a common type of formulations, and therefore changes in the drug-release rate over time may also cause severe toxicity as well as adverse side effects on therapeutic effects for patients.
  • sustained-release formulations As discussed above, even though a very important factor contemplated for the design of sustained-release formulations is to secure the stability over time of the drug-release rate, efforts for this purpose are still poorly made hitherto. Generally, since materials used for moisture-proof coating have effects to some extent on the release of drugs, selection of materials added for securing of moisture-proofness may be a critical technology in the sustained-release formulations that require elaborate control of the drug-release rate. In the present invention, it was possible to significantly improve the stability of a pellet formulation during storage and distribution thereof, while not having significant effects on the drug-release rate, by coating the controlled-release pellet containing tolterodine with Eudragit E or AEA which has been conventionally used to mask bitter taste.
  • the pellet formulation is advantageous to reduce between- and within-patient variability in drug efficacy, because a pharmaceutical formulation in the form of a pellet exhibits low variability in the drug-release rate due to various in vivo factors such as gastrointestinal motility in patients, as compared to a matrix tablet formulation.
  • a pellet form of the pharmaceutical formulation has a large surface area that is exposed to external factors such as moisture and light, as compared to a matrix form that is formulated into a tablet.
  • pellet formulation suffers from the high risk of changes in the drug-release rate over time in response to storage conditions because a controlled-release layer formed of a hydrophobic polymer alone or in admixture with a hydrophilic polymer is usually employed instead of using gelation of hydrophilic polymers.
  • a controlled-release layer formed of a hydrophobic polymer alone or in admixture with a hydrophilic polymer is usually employed instead of using gelation of hydrophilic polymers.
  • controlled-release formulations inter alia sustained-release formulations contain large quantities of drug substances as compared to common formulations, and therefore it is very important to ensure the stability over time since they may cause severe toxicity to patients when changes in the drug-release rate over time occur due to storage conditions.
  • the present invention is intended to secure the stability over time for a sustained-release formulation in the form of a pellet having noticeable advantages, due to low between- and within-patient variability in drug efficacy, as compared to the tablet in the form of a matrix.
  • the present invention has employed a controlled-release pellet composition comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material; (ii) a first layer on the core unit of a substantially water-insoluble polymer wherein the first layer is adapted to control water penetration into the core; (iii) a second layer covering the first layer and containing an active ingredient; and (iv) a third layer of polymer on the second layer effective for controlled release of the active ingredient, which was known in Korean Patent Registration No.
  • a novel controlled-release pellet composition comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material or wax; (ii) a first layer covering the core unit and containing an active ingredient; and (iii) a second layer of polymer on the first layer effective for controlled release of the active ingredient, without formation of a layer adapted to control water penetration into the core, which was independently developed by present inventors.
  • Eudragit E or AEA which is insoluble at a pH of moisture in the atmosphere, i.e., pH 5.5 or higher, was selected as a coating material for the composition. Since the pH of the stomach in vivo is typically regarded as having a value of 1.2, the layer added to ensure the stability over time may be readily degraded in the stomach upon administration of the composition according to the present invention. That is, due to rapid degradation and disappearance of the moisture-proof layer in the stomach after administration of the composition, it is possible to secure the same drug-release rate as in the controlled-release pellet containing no moisture-proof layer.
  • FIG. 1 is a graph comparing a drug-release rate between a conventional controlled-release pellet (Example 1) and the same ones coated with Eudragit E (Example 3) and AEA (Example 4) of the present invention;
  • FIG. 2 is a graph comparing a drug-release rate between a novel controlled-release pellet of the present invention (Example 2), and the same ones coated with Eudragit E (Example 5) or AEA (Example 6) of the present invention;
  • FIG. 3 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 1 and 3, respectively;
  • FIG. 4 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 2 and 5, respectively;
  • FIG. 5 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 1 and 4, respectively;
  • FIG. 6 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 2 and 6, respectively; and FIG. 7 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 7 and 8, respectively.
  • the present invention is characterized by coating of a sustained-release pellet with a dimethylaminoethyl methacrylate/methyl methacrylate copolymer (Eudragit E) or polyvinylacetal diethylaminoacetate (AEA) which is insoluble at a pH of 5.5 or higher, thereby securing the stability of a sustained-release pellet.
  • a sustained-release pellet with a dimethylaminoethyl methacrylate/methyl methacrylate copolymer (Eudragit E) or polyvinylacetal diethylaminoacetate (AEA) which is insoluble at a pH of 5.5 or higher, thereby securing the stability of a sustained-release pellet.
  • the present invention may use a controlled-release pellet composition
  • a controlled-release pellet composition comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material; (ii) a first layer on the core unit of a substantially water-insoluble polymer wherein the first layer is adapted to control water penetration into the core; (iii) a second layer covering the first layer and containing an active ingredient; and (iv) a third layer of polymer on the second layer effective for controlled release of the active ingredient, which was known in Korean Patent Registration No.
  • a novel controlled-release pellet composition comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material or wax; (ii) a first layer covering the core unit and containing an active ingredient; and (iii) a second layer of polymer on the first layer effective for controlled release of the drug, without inclusion of a layer for control of water penetration into the core, which was independently developed by present inventors.
  • the present invention has been made in view of the above problems, and it is an object of the present invention to provide a novel controlled-release pellet comprising:
  • the controlled-release pellet of the present invention is characterized by the drug-release rate of more than 80% after 18 hours, for the drug present on the first layer.
  • the controlled-release pellet having the stability over time according to the present invention is characterized by the drug-release rate of less than 60% after 24 hours, as measured according to the drug-release test in 900 mL of a phosphate buffer solution (pH 6.8) as the dissolution medium, using the USP apparatus 1 at 37 " C and 100 rpm.
  • the novel controlled-release composition which was developed by present inventors, is prepared to have a first layer containing an active drug ingredient and a second layer for controlled release of the drug from the first layer.
  • a first layer containing an active drug ingredient
  • a second layer for controlled release of the drug from the first layer.
  • the drug ingredient is mixed with a water-soluble polymer to thereby prepare a first layer.
  • a second layer adapted to control drug release of the first layer is prepared using water-insoluble polymer, a polymer having pH-dependent solubility and a water-soluble polymer alone or in combination thereof. That is, unlike the prior art conventional composition known in Korean Patent Registration No. 10-0467384, the composition of the present invention is a novel pellet composition which is capable of achieving excellent drug-release profile even without formation of a layer for control of water penetration into the core.
  • the controlled-release preparation is defined as a pharmaceutical formulation that contains tolterodine, a tolterodine compound or a pharmaceutically acceptable salt thereof as a drug of interest, and exhibits a drug- release rate of 10 to 40% at a 2 hour-time point and a drug-release rate of more than 80% at a final 18 hour-time point, when the drug-release test of the test sample was carried out in 900 mL of a first solution as the dissolution medium (as listed in the Korean Pharmacopoeia, 8th edition) using the USP apparatus 1 at 37 ° C and 100 rpm for 2 hours, and then in 900 mL of a phosphate buffer solution (pH 6.8) for 16 hours (the total of 18-hour test period including the test in the first solution).
  • the controlled-release preparation of the present invention also encompasses semi-products that may be produced in the intermediate process during manufacturing of the pharmaceutical formulation.
  • materials that can be used as core materials in the present invention are spheres of sucrose/starch (Sugar Spheres NF), sucrose crystals, or extruded and dried spheres comprised of typical excipients such as microcrystalline cellulose and lactose, which are known to those skilled in the art and are pharmaceutically acceptable seeds.
  • materials having a particle size of 0.3 to 1.7 mm are used as the core material.
  • a water-soluble or water-swellable inert material that can be used in the present invention
  • saccharides such as sucrose, mannitol, sorbitol and lactose
  • starches such as potato starch and corn starch
  • celluloses such as hydroxyethylcellulose and microcrystalline cellulose, and any combination thereof.
  • pharmaceutically commonly used materials such as white wax, camauba wax and microcrystalline wax may be used as the seed.
  • the seed containing carnauba wax and having a particle size of 0.3 to 1.7 mm is most suitable as the core.
  • Examples of the drug substance constituting the first layer include tolterodine, tolterodine compounds and pharmaceutically acceptable salts thereof.
  • Examples of the polymers that are used in admixture with the drug substance of interest may include polyvinylpyrrolidone (PVP), polyalkylene glycol such as polyethylene glycol, gelatin, polyvinyl alcohol, starch and derivatives thereof, cellulose derivatives such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxyethyl cellulose and carboxymethylhydroxyethyl cellulose, acrylic acid polymers, polymers of methacrylic acid and methacrylate (such as Eudragit L100-55, L30 D-55, L12.5, LlOO, S12.5, SlOO, and FS 30D), hydroxypropylmethylcellulose phthalate and any other pharmaceutically acceptable polymers.
  • the second layer is a layer that is formed of a water-insoluble polymer alone or in conjunction with the addition of a water-soluble polymer, adapted to control drug release in the controlled-release preparation of the present invention.
  • the water-insoluble polymers that can be utilized in the present invention may include water-insoluble materials conventionally used in the art, such as hydroxyethylcellulose, methylcellulose, ethylcellulose, polymers of methacrylic acid and methacrylate (such as Eudragit RS 12.5, RS 100, RS PO, RS 30D, RL 12.5, RL 100, RL PO, RL 30D, NE 30D, NE 4OD, L1OO-55, L30D- 55, L12.5, LlOO, S12.5, SlOO, FS 30D, E12.5, ElOO, and E PO), polyethylene, polyamide, poly(ethylene-vinylacetate), cellulose nitrate, silicone, and poly(lactide-co-glycolide).
  • water-soluble polymers added for controlled release of drugs may include water-soluble polymers that are conventionally used in pharmaceutical chemistry, such as polyethylene glycol, polyethylene oxide, carboxymethylcellulose, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose and polyvinyl alcohol, and saccharides such as sucrose, lactose, mannitol and sorbitol.
  • the second layer may include a plasticizer that is typically used in pharmaceutical chemistry.
  • the ratio of the film-forming, water-insoluble polyme ⁇ water-soluble polymer may vary depending upon kinds and characteristics of polymers to be used.
  • the coating amount is set to a range capable of maintaining the drug-release rate of less than 60%, when the release rate of the drug on the first layer of the coated pellet is measured in 900 mL of a phosphate buffer solution (pH 6.8) as the dissolution medium, using the USP apparatus 1 at 37 ° C and 100 rpm for 24 hours.
  • the present invention is characterized in that the pharmaceutical composition should have the improved stability over time for the controlled-release pellet, by always exhibiting the drug- release rate of less than about 60% as measured according to the above-mentioned drug release test.
  • the scope of products showing such a drug-release profile also encompasses semi-products which are produced during the manufacturing process of the controlled-release preparation containing tolterodine, a tolterodine compound or a pharmaceutically acceptable salt thereof.
  • Example 1 Pellets of Example 1 were coated with a solution of 1.09 kg of dimethylaminoethyl methacrylate/methyl methacrylate copolymer (Eudragit E) dissolved in 10.0 kg of 80% ethanol.
  • Eudragit E dimethylaminoethyl methacrylate/methyl methacrylate copolymer
  • Example 1 Pellets of Example 1 were coated with a solution of 219 g of polyvinylacetal diethylaminoacetate (AEA) dissolved in 1.5 kg of 80% ethanol.
  • AEA polyvinylacetal diethylaminoacetate
  • Example 5 Pellets of Example 2 were coated with a solution of 900 g of Eudragit E dissolved in 6.0 kg of 80% ethanol.
  • Example 7 Pellets of Example 2 were coated with a solution of 180.0 g of AEA dissolved in 1.5 kg of 80% ethanol.
  • Example 7
  • Example 7 Pellets of Example 7 were coated with a solution of 180.0 g of AEA dissolved in 1.5 kg of 80% ethanol.
  • the drug-release test of the-thus obtained capsule was carried out in 900 mL of a first solution as the dissolution medium (as listed in the Korean Pharmacopoeia, 8th edition), using the USP apparatus 1 at 37 ° C and 100 rpm for 2 hours, and then in 900 mL of a phosphate buffer solution (pH 6.8) for 16 hours (total of 18-hour test period including the test in the first solution). Thereafter, the drug-release rate of the test sample was calculated at each time point.
  • FIG. 1 is a graph comparing a drug-release rate between a conventional controlled-release pellet (Example 1), and the same ones coated with Eudragit E (Example 3) and AEA (Example 4) of the present invention.
  • FIG. 2 is a graph comparing a drug-release rate between a novel controlled-release pellet of the present invention (Example 2), and the same ones coated with Eudragit E (Example 5) and AEA (Example 6) of the present invention.
  • FIG. 3 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 1 and 3.
  • FIG. 4 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 2 and 5.
  • FIG. 5 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 1 and 4.
  • FIG. 6 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 2 and 6.
  • FIG. 7 is a graph showing evaluation results of the stability over time of pellets prepared in Examples 7 and 8.
  • the present invention provides a novel pharmaceutical composition which is capable of improving the stability over time of a drug pellet during storage and distribution of the pellet having controlled-release properties. More specifically, the present invention relates to a novel pharmaceutical composition which is capable of preventing moisture- induced changes in a drag-release rate during storage and distribution of a drug pellet, via coating of a controlled-release pellet, comprising tolterodine, a tolterodine compound or a pharmaceutically acceptable salt thereof as a drug of interest, with Eudragit E or polyvinylacetal diethylaminoacetate (hereinafter, referred to as "AEA") which is insoluble at a pH of 5.5 or higher.
  • Eudragit E or polyvinylacetal diethylaminoacetate hereinafter, referred to as "AEA" which is insoluble at a pH of 5.5 or higher.

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Abstract

L'invention porte sur une nouvelle composition pharmaceutique améliorant la stabilité dans le temps de comprimés de médicaments pendant leur stockage et leur libération contrôlée, et plus spécifiquement sur une nouvelle composition pharmaceutique prévenant grâce à un enrobage les variations sous l'effet de l'humidité du taux de libération lors du stockage et de la distribution d'un comprimé et plus particulièrement d'un comprimé à libération continue contenant de la toltérodine. L'invention porte également sur un composé de toltérodine ou de l'un de ses sels pharmacocompatible et d'un copolymère de diméthylaminoéthyl méthacrylate/méthyl méthacrylate (dit ci-après 'Eudragit E') ou de polyvinylacétal diéthylaminoacétate (dit ci-après 'AEA') insoluble pour un pH de 5,5 ou plus.
PCT/KR2006/002764 2005-07-22 2006-07-14 Comprimes stables a liberation controlee contenant de la tolterodine WO2007011131A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2005-0066604 2005-07-22
KR20050066604 2005-07-22

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Cited By (7)

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EP1810668A1 (fr) * 2006-01-23 2007-07-25 LEK Pharmaceuticals D.D. Compositions pharmaceutiques enrobées à base de tartrate de toltérodine
WO2008012346A1 (fr) * 2006-07-28 2008-01-31 Farmaprojects, S. A. Préparation pharmaceutique de métoprolol à libération prolongée et son procédé de préparation
WO2009003724A1 (fr) * 2007-07-03 2009-01-08 Synthon B.V. Bille de toltérodine
WO2009019599A3 (fr) * 2007-08-08 2009-04-09 Themis Lab Private Ltd Compositions à libération prolongée comprenant de la toltérodine
GR1006406B (el) * 2008-05-06 2009-05-26 Specifar Abee ���������� ������� ��� ������������� ��������� Μικροδισκια παρατεταμενης αποδεσμευσης της τρυγικης τολτεροδινης
WO2009140557A2 (fr) * 2008-05-14 2009-11-19 Capricorn Pharma, Inc. Formulations de toltérodine à libération modifiée
US8686403B2 (en) 2008-01-18 2014-04-01 Lg Chem Ltd. Organic luminescent device including a first electrode, two or more organic layers and a second electrode and a production method for the same

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WO2003053428A1 (fr) * 2001-12-20 2003-07-03 Pharmacia Corporation Forme posologique de liberation a controlee possedant des proprietes ameliorees de liberation de medicaments
US6770295B1 (en) * 1998-08-27 2004-08-03 Pharmacia Ab Therapeutic formulation for administering tolterodine with controlled release
WO2004105735A1 (fr) * 2003-05-30 2004-12-09 Ranbaxy Laboratories Limited Compositions pharmaceutiques de tolterodine a liberation controlee et leurs procedes de preparation
WO2005105036A1 (fr) * 2004-04-28 2005-11-10 Natco Pharma Limited Matrice muco-adhesive a liberation controlee contenant de la tolterodine, et procede d'elaboration

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6770295B1 (en) * 1998-08-27 2004-08-03 Pharmacia Ab Therapeutic formulation for administering tolterodine with controlled release
WO2003053428A1 (fr) * 2001-12-20 2003-07-03 Pharmacia Corporation Forme posologique de liberation a controlee possedant des proprietes ameliorees de liberation de medicaments
WO2004105735A1 (fr) * 2003-05-30 2004-12-09 Ranbaxy Laboratories Limited Compositions pharmaceutiques de tolterodine a liberation controlee et leurs procedes de preparation
WO2005105036A1 (fr) * 2004-04-28 2005-11-10 Natco Pharma Limited Matrice muco-adhesive a liberation controlee contenant de la tolterodine, et procede d'elaboration

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1810668A1 (fr) * 2006-01-23 2007-07-25 LEK Pharmaceuticals D.D. Compositions pharmaceutiques enrobées à base de tartrate de toltérodine
WO2007082770A1 (fr) * 2006-01-23 2007-07-26 Lek Pharmaceuticals D.D. Formules enrobées
WO2008012346A1 (fr) * 2006-07-28 2008-01-31 Farmaprojects, S. A. Préparation pharmaceutique de métoprolol à libération prolongée et son procédé de préparation
WO2009003724A1 (fr) * 2007-07-03 2009-01-08 Synthon B.V. Bille de toltérodine
WO2009019599A3 (fr) * 2007-08-08 2009-04-09 Themis Lab Private Ltd Compositions à libération prolongée comprenant de la toltérodine
US8871275B2 (en) 2007-08-08 2014-10-28 Inventia Healthcare Private Limited Extended release compositions comprising tolterodine
US8686403B2 (en) 2008-01-18 2014-04-01 Lg Chem Ltd. Organic luminescent device including a first electrode, two or more organic layers and a second electrode and a production method for the same
GR1006406B (el) * 2008-05-06 2009-05-26 Specifar Abee ���������� ������� ��� ������������� ��������� Μικροδισκια παρατεταμενης αποδεσμευσης της τρυγικης τολτεροδινης
WO2009135520A1 (fr) * 2008-05-06 2009-11-12 Specifar S.A. Microcomprimés à libération prolongée comportant du tartrate de toltérodine
WO2009140557A2 (fr) * 2008-05-14 2009-11-19 Capricorn Pharma, Inc. Formulations de toltérodine à libération modifiée
WO2009140557A3 (fr) * 2008-05-14 2010-01-07 Capricorn Pharma, Inc. Formulations de toltérodine à libération modifiée

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