WO1996012477A1 - Systeme d'administration orale a liberation lente contenant de l'oxybutynine - Google Patents

Systeme d'administration orale a liberation lente contenant de l'oxybutynine Download PDF

Info

Publication number
WO1996012477A1
WO1996012477A1 PCT/FI1994/000474 FI9400474W WO9612477A1 WO 1996012477 A1 WO1996012477 A1 WO 1996012477A1 FI 9400474 W FI9400474 W FI 9400474W WO 9612477 A1 WO9612477 A1 WO 9612477A1
Authority
WO
WIPO (PCT)
Prior art keywords
oxybutynin
weight
delivery system
controlled release
hydrophilic material
Prior art date
Application number
PCT/FI1994/000474
Other languages
English (en)
Inventor
Pertti Rantala
Original Assignee
Leiras Oy
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8556592&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1996012477(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Leiras Oy filed Critical Leiras Oy
Priority to PCT/FI1994/000474 priority Critical patent/WO1996012477A1/fr
Priority to AU79946/94A priority patent/AU7994694A/en
Publication of WO1996012477A1 publication Critical patent/WO1996012477A1/fr

Links

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
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
    • 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
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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

Definitions

  • the present invention relates to controlled or extended release delivery systems for the treatment of disorders responsive to the action of an antispasmodically active agents, especially for the treatment of a neurogenic bladder, a method of preparation of the delivery systems as well as method of using them.
  • Oxybutynin and its salts, in particular the hydrochloride is a musculotropic antispasmodic drug with moderate anticholinergic, systemic analgesic and local anaesthetic action. Its relaxant effect on smooth muscle is based on antagonism of a process distal to the neuromuscular junction (papaverine-like effect) and on anticholinergic action on the blockage of muscari- ne-type receptors.
  • Oxybutynin chloride has been in clini ⁇ cal use for twenty years and it is indicated for the re ⁇ lief of symptoms associated with voiding in patients with an uninhibited neurogenic and reflex neurogenic bladder.
  • the drug is also used to suppress gastric acid secretion, to relieve post-transurethral vesical pain and spasm in the gastrointestinal tract, to control detrusor dysfunction and to facilitate catheterization of the urinary bladder in myelomeningocele patients.
  • the drug is effective when given orally.
  • oxybutynin hydrochloride (DL-racemic form of 4-diethylamino-2-butynyl-phenyl-cyclohexylglycolate hy- drochloride) is a tertiary amine. It is rapidly absorbed from the gastrointestinal tract following oral admini ⁇ stration and its pharmacological action starts within one hour. The duration of action of the drug is three to six hours.
  • the afore mentioned aim has been reached by combining oxybutynin or a pharmaceutical ⁇ ly acceptable salt thereof, with an excipient allowing the controlled and extended, even release of the active agent over a period of time exceeding 24 hours while si- ultaneously reducing the initial peak concentrations of active agent in the blood of the patient.
  • the invention provides a controlled release oral delivery system for the treatment of disorders responsive to the action of an antispasmodically active agent, comp ⁇ rising
  • a hydrophilic material comprising a heteropolysaccharide and a homopo- lysaccharide, in a ratio of about 1:3 to 3:1
  • the excipient used in the composition according to the invention thus comprises as one component a hydrophilic material or gelling system comprising on the hand a hete ⁇ ropolysaccharide, and on the other hand a homopolysaccha ⁇ ride which is capable of crosslinking the heteropolysac ⁇ charide in an aqueous fluid, such as in a gastric fluid, the ratio between the two types of saccharides being from about 3:1 to 1:3.
  • the heteropolysaccharide is a water soluble saccharide containing two or more kinds of sugar units, and it has excellent swelling properties. According to a preferred embodiment it comprises a xanthan gum, or a derivative thereof. Such derivatives are deacylated xanthan gum, the carboxymethyl ether and propylene glycol ester.
  • the homopolysaccharide comp- rises one or more galactomannans, and especially galacto- mannas with a higher ratio of mannose to galactose, e.g. locust bean gum.
  • Other polysaccharides are e.g. guar gum and hydroxypropyl guar gum.
  • the ratio between heteropolysaccharide and homopolysacha- ride is preferably approximately 1:1.
  • the excipient contains an inert filler or diluent, which suitably is a monosaccharide, disaccharid or polyhydric alcohol, such as sucrose, dextrose, lacto ⁇ se, fructose, xylitol, sorbitol, and microcrystalline cellulose, or mixtures thereof.
  • the excipient used in the composition according to the invention contains in addition a cationic crosslinking agent which is capable of crosslinking the hydrophilic material, when this is exposed to gastrointestinal fluids, thus strengthening the gel structure and preven ⁇ ting an initial burst of the drug when exposed to a ga ⁇ strointestinal environment.
  • the amount of cationic cross linking is at the most about 20 % by weight, such as fro bout 1 to 20, especially about 5 to 15 % by weight.
  • the cationic crosslinking agent can be a mono- or multi- valent salt, preferably an inorganic salt such as alkali and/or alkaline earth metal salt, such as sodium, potassium, litiu , calcium, magnesium chloride, bromide, sulfate, borate, citrate, acetate, lactate, carbonate, bicarbonate.
  • the cationic crosslinking agent is prefera ⁇ bly divalent, such as in calcium sulfate, or it is sodiu chloride.
  • the excipient contains about 2 to 50, especially about 25 to 35 % by weight of the hyd ⁇ rophilic material or gelling system, about 5 to 15 % by weight of cationic crosslinking agents, and about 35 to 70, especially about 50 to 70 % by weight of inert di ⁇ luent.
  • the ratio of oxybutynin (calculated as its hydrochloride) to hydrophilic material is preferably about 1:5 to 1:15.
  • a suitable amount of oxybutynin in a single dose, such as in a tablet, is about 5 to 20 mg, especially about 10 mg.
  • a suitable daily dose of opxybutynin is from about 0.05 to 0.25 mg/kg body weight, especially appr. 0.12 mg/kg body weight.
  • the drug delivery system according to the invention can be made by first dry blending the ingredients for the excipient, and then granulating the mixture in the pre ⁇ sence of small amount of fluid, such as water.
  • the ob ⁇ tained granulate is therafter combined with the active ingredient for example by simple dry-blending, or by using wet granulation techniques, using e.g. water as the granulating fluid.
  • a suitable lubricant known per se, can be added to the excipient and drug components to be combined.
  • the choice of lubri ⁇ cants is well known in the art, and magnesium, calcium and sodium stearate may be mentioned.
  • a suitable amount of lubricant is appr. 0,5 to 3 % by weight.
  • the drug-excipient mixture prepared may be compressed to tablets according to conventional tablet formation tech ⁇ niques.
  • the blend may also be used as pellets, as a gra ⁇ nulate or powder, or filled in capsules.
  • the dosage for ⁇ med obtained may be coated using any suitable coating system. Such coating systems and coating techniques are well known in the art.
  • compositions further agents and additives, e.g. hydropho- bic agents for regulating the hydration of the product, for example by including polymeric cellulose derivatives, such as alkyl celluloses, polymeric acrylic and methacry- lie acid derivatives, waxes, oils etc. usually in amounts amounting to about 1 to 20 % by weight.
  • polymeric cellulose derivatives such as alkyl celluloses, polymeric acrylic and methacry- lie acid derivatives, waxes, oils etc.
  • hydrophobic agents are as such well known in the art, and a number of them are commercially available.
  • release rate decreasing substances to the mixture of drug and excipient, for example microcrystalline cellulo ⁇ se in an amount of about 1 to 10 % by weight.
  • the present invention also concerns a method for treating a subject of a condition responsive to the action of an antispasmodically active agent, such as voiding resulting from uninhibited or reflex neurogenic bladder, gastric acid secretion, vesical pain, gastrointestinal tract spasm and detruson dysfunction, especially of neurogenic bladder, the method comprising administering to the sub ⁇ ject for oral ingestion a delivery system, especially a tablet, according to the invention as defined above.
  • an antispasmodically active agent such as voiding resulting from uninhibited or reflex neurogenic bladder, gastric acid secretion, vesical pain, gastrointestinal tract spasm and detruson dysfunction, especially of neurogenic bladder
  • the invention also concerns a method of maintaining, in a human subject, a therapeutically sufficient blood level concentration of oxybutynin or of an active metabolite thereof, such as N-desethyl oxybutynin, for an extended period of time, the method comprising administering oral- ly to the said subject a controlled release delivery sys ⁇ tem according to the invention, as defined above, espe ⁇ cially a tablet containing 5 to 20 mg of oxybutynin.
  • a therapeutically sufficient blood level concent ⁇ ration is maintained for at least about 24 hours after administration of a single dose of oxybutynin, such as a single dose of about 0.05 mg/kg to 0.25 mg/kg, especially about 0.12 mg/kg body weight, of oxybutynin or a salt thereof, e.g. the hydrochloride.
  • the administration of a daily single dose of a 10 mg controlled release oxybuty- nin tablet gave blood level concentrations of oxybutynin of at least about 0.5 ng/ml, such as 0.5 to 2.0 ng/ml for a period of at least about 24 hours, the value following the peak value being in the area of about 0.5 to 1.0 ng/ml, as is evident from the test report.
  • Examples 1-2 controlled release excipients in accor ⁇ dance with the present invention were first prepared, the oxybutynin being added subsequently, and the final mixtu ⁇ re then being tableted.
  • the excipient was prepared by dry blending the requisite amounts of xanthan gum, locust bean gum, calcium sulfate, and dextrose in a high speed mixer/granulater for 2 minu ⁇ tes. While running choppers/impellers, the requisite amount of water was added to the dry blended mixture, and granulated for another 2 minutes. The granulation was then dried in a fluid bed dryer to a LOD (loss on drying) of less than about 10% by weight (e.g. 4-7% LOD) . The granulation was then milled using 20 mesh screens.
  • the ingredients of the granulations of Examples 1-2 are set forth in Table 1 below:
  • Examples 3-4 a controlled release excipient was pre ⁇ pared in accordance with the procedures set forth for Examples 1-2.
  • the ingredients of the sustained release matrix of Examples 3-4 are set forth in Table 3 below:
  • Example 3 the drug:gel ratio is about 1:10. In Example 4, the drug:gel ratio is about 1:5.
  • gel it is meant the combined weight of xanthan gum and locust bean gum.
  • a bioequivalence study was carried out to assess the bio ⁇ availability of oxybutynin from a delivery system accor- ding to the invention, using as a reference system an ordinary 5 mg oxybutynin chloride containing tablet, af ⁇ ter a single peroral dose of 10 mg of oxybutynin chlori ⁇ de.
  • the study was performed as a balanced, randomized, three- period cross-over study on 24 healthy volunteers.
  • the pharmacokinetic parameters were calculated and curves created using the Siphar program.
  • All urine excreted during 24 h after administration of the drug was collected as follows: one sample was taken before administration (blank sample) ; thereafter, samples in fractions of four hours up to 12.0 h after administra- tion (0.0-4.0 h, 4.0-8.0 h and 8.0-12.0 h) , and in a fraction of twelve hours up to 24.0 h (12.0-24.0 h) .
  • Urine fractions were measured by volume, and aliquots of 2-3 ml separated into duplicate polypropylene tubes, fro- zen immediately and stored at -20°C for later examinati ⁇ on.
  • N-desethyl oxy ⁇ butynin in serum were carried out by a capillary gas chromatographic method using mass selective detector.
  • the quantification limit of the method was 0.2 ng/ml for un ⁇ changed oxybutynin and 2.5 ng/ml for the metabolite.
  • the method is linear from 0.2 ng/ml to 30 ng/ml for oxy ⁇ butynin and from 2.5 to 150 ng/ml for N-desethyl oxy ⁇ butynin, respectively.
  • Fig. 1 shows the mean serum concentra ⁇ tion of oxybutynin as a function of time after adminis- tartion of a 10 mg controlled release tablet of the in- vention, and 2 * 5 mg conventional tablets.
  • Fig. 2 shows the serum concentration of the metabolite, N-desethyl oxybutynin after the said administration.
  • the controlled release tablet of the invention gave a reliable pharmacokinetic profile of an extended release formulation covering the 24-hour study period.
  • the controlled release tablet can be considered a suc ⁇ cessful and clinically bioequivalent formulation when lower peak concentrations of oxybutynin in serum are de ⁇ sirable to diminish anticholinergic side-effects of oxy ⁇ butynin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Système d'administration d'oxybutynine à libération lente, préparation et utilisation dudit système. Ledit système d'administration de médicament comporte de l'oxybutynine en association avec un excipient à libération lente contenant 20 à 60 % en poids d'un matériau hydrophile renfermant un hétéropolysaccharide et un homopolysaccharide, dans un rapport de 1/3 à 3/1, un agent de réticulation cationique pour ledit matériau hydrophile en une quantité comprise entre 1 et 20 % en poids, et 20 à 79 % en poids d'une charge inerte.
PCT/FI1994/000474 1994-10-21 1994-10-21 Systeme d'administration orale a liberation lente contenant de l'oxybutynine WO1996012477A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/FI1994/000474 WO1996012477A1 (fr) 1994-10-21 1994-10-21 Systeme d'administration orale a liberation lente contenant de l'oxybutynine
AU79946/94A AU7994694A (en) 1994-10-21 1994-10-21 Controlled release oral delivery system containing oxybutynin

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/FI1994/000474 WO1996012477A1 (fr) 1994-10-21 1994-10-21 Systeme d'administration orale a liberation lente contenant de l'oxybutynine

Publications (1)

Publication Number Publication Date
WO1996012477A1 true WO1996012477A1 (fr) 1996-05-02

Family

ID=8556592

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI1994/000474 WO1996012477A1 (fr) 1994-10-21 1994-10-21 Systeme d'administration orale a liberation lente contenant de l'oxybutynine

Country Status (2)

Country Link
AU (1) AU7994694A (fr)
WO (1) WO1996012477A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998001125A2 (fr) * 1996-07-09 1998-01-15 Sepracor, Inc. Isomeres dextrogyres d'oxybutynine et de desethyloxybutynine utilises dans le traitement de l'hyperactivite gastro-intestinale
WO1999048494A1 (fr) * 1998-03-26 1999-09-30 Alza Corporation Composition d'oxybutine a liberation continue et effet de xerostomie reduit
WO2000012069A1 (fr) 1998-08-27 2000-03-09 Pharmacia & Upjohn Ab Formulation de tolterodine therapeutique a liberation controlee
WO2000019997A1 (fr) * 1998-10-07 2000-04-13 Alza Corporation Forme posologique a liberation controlee renfermant de l'oxybutynine
US6171298B1 (en) 1996-05-03 2001-01-09 Situs Corporation Intravesical infuser
US6248359B1 (en) 2000-01-05 2001-06-19 Laboratorios Phoenix U.S.A., Inc. Multi-tablet oxybutynin system for treating incontinence
US6262115B1 (en) 1995-05-22 2001-07-17 Alza Coporation Method for the management of incontinence
US6630162B1 (en) 1999-11-11 2003-10-07 Pharmacia Ab Pharmaceutical formulation and its use
US7230030B2 (en) 1998-05-12 2007-06-12 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US7862552B2 (en) 2005-05-09 2011-01-04 Boston Scientific Scimed, Inc. Medical devices for treating urological and uterine conditions
US7943176B2 (en) 2001-10-09 2011-05-17 Apogepha Arzneimittel Gmbh Oral dosage form for propiverine or its pharmaceutically acceptable salts with an extended release of the active ingredient
US7989654B2 (en) * 2003-04-08 2011-08-02 Ucb Pharma Gmbh High purity bases of 3,3-diphenylpropylamino monoesters
US8241667B2 (en) 2001-11-06 2012-08-14 Osmotica Kereskedelmi és Szolgáltató KFT Dual controlled release osmotic device
US8329217B2 (en) 2001-11-06 2012-12-11 Osmotica Kereskedelmi Es Szolgaltato Kft Dual controlled release dosage form

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5135757A (en) * 1988-09-19 1992-08-04 Edward Mendell Co., Inc. Compressible sustained release solid dosage forms
EP0497977A1 (fr) * 1989-10-26 1992-08-12 Nippon Shinyaku Company, Limited Preparation gastrique
US5169639A (en) * 1988-09-19 1992-12-08 Edward Mendell Co., Inc. Controlled release verapamil tablets
US5399359A (en) * 1994-03-04 1995-03-21 Edward Mendell Co., Inc. Controlled release oxybutynin formulations

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5135757A (en) * 1988-09-19 1992-08-04 Edward Mendell Co., Inc. Compressible sustained release solid dosage forms
US5169639A (en) * 1988-09-19 1992-12-08 Edward Mendell Co., Inc. Controlled release verapamil tablets
EP0497977A1 (fr) * 1989-10-26 1992-08-12 Nippon Shinyaku Company, Limited Preparation gastrique
US5399359A (en) * 1994-03-04 1995-03-21 Edward Mendell Co., Inc. Controlled release oxybutynin formulations

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6919092B2 (en) 1995-05-22 2005-07-19 Alza Corporation Method for the management of incontinence
US6262115B1 (en) 1995-05-22 2001-07-17 Alza Coporation Method for the management of incontinence
US6171298B1 (en) 1996-05-03 2001-01-09 Situs Corporation Intravesical infuser
WO1998001125A2 (fr) * 1996-07-09 1998-01-15 Sepracor, Inc. Isomeres dextrogyres d'oxybutynine et de desethyloxybutynine utilises dans le traitement de l'hyperactivite gastro-intestinale
WO1998001125A3 (fr) * 1996-07-09 1998-05-07 Sepracor Inc Isomeres dextrogyres d'oxybutynine et de desethyloxybutynine utilises dans le traitement de l'hyperactivite gastro-intestinale
WO1999048494A1 (fr) * 1998-03-26 1999-09-30 Alza Corporation Composition d'oxybutine a liberation continue et effet de xerostomie reduit
US7384980B2 (en) 1998-05-12 2008-06-10 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US7230030B2 (en) 1998-05-12 2007-06-12 Schwarz Pharma Ag Derivatives of 3,3-diphenylpropylamines
US8338478B2 (en) 1998-05-12 2012-12-25 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
US7855230B2 (en) 1998-05-12 2010-12-21 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
US7985772B2 (en) 1998-05-12 2011-07-26 Ucb Pharma Gmbh Derivatives of 3,3-diphenylpropylamines
BG65168B1 (bg) * 1998-08-27 2007-05-31 Pharmacia Ab Фармацевтична форма на толтеродин с контролирано освобождаване
AP1529A (en) * 1998-08-27 2006-01-03 Pharmacia & Upjohn Ab Therapeutic formulation for administering tolterodine with controlled release.
WO2000012069A1 (fr) 1998-08-27 2000-03-09 Pharmacia & Upjohn Ab Formulation de tolterodine therapeutique a liberation controlee
US6770295B1 (en) 1998-08-27 2004-08-03 Pharmacia Ab Therapeutic formulation for administering tolterodine with controlled release
EP2153825A1 (fr) 1998-08-27 2010-02-17 Pfizer Health AB Formulation de tolterodine therapeutique a liberation controlee
AU745190B2 (en) * 1998-08-27 2002-03-14 Pharmacia & Upjohn Ab Therapeutic formulation for administering tolterodine with controlled release
CZ302630B6 (cs) * 1998-08-27 2011-08-10 Pharmacia & Upjohn Ab Farmaceutický prostredek obsahující tolterodin nebo tolterodinu príbuznou slouceninu
WO2000019997A1 (fr) * 1998-10-07 2000-04-13 Alza Corporation Forme posologique a liberation controlee renfermant de l'oxybutynine
US6630162B1 (en) 1999-11-11 2003-10-07 Pharmacia Ab Pharmaceutical formulation and its use
US6248359B1 (en) 2000-01-05 2001-06-19 Laboratorios Phoenix U.S.A., Inc. Multi-tablet oxybutynin system for treating incontinence
US7943176B2 (en) 2001-10-09 2011-05-17 Apogepha Arzneimittel Gmbh Oral dosage form for propiverine or its pharmaceutically acceptable salts with an extended release of the active ingredient
US8241667B2 (en) 2001-11-06 2012-08-14 Osmotica Kereskedelmi és Szolgáltató KFT Dual controlled release osmotic device
US8329217B2 (en) 2001-11-06 2012-12-11 Osmotica Kereskedelmi Es Szolgaltato Kft Dual controlled release dosage form
US8591947B2 (en) 2001-11-06 2013-11-26 Osmotica Kereskedelmi és Szolgáltató KFT Dual controlled release dosage form
US7989654B2 (en) * 2003-04-08 2011-08-02 Ucb Pharma Gmbh High purity bases of 3,3-diphenylpropylamino monoesters
US7862552B2 (en) 2005-05-09 2011-01-04 Boston Scientific Scimed, Inc. Medical devices for treating urological and uterine conditions

Also Published As

Publication number Publication date
AU7994694A (en) 1996-05-15

Similar Documents

Publication Publication Date Title
US20210008063A1 (en) Oxymorphone controlled release compositions
US8329216B2 (en) Oxymorphone controlled release formulations
US7276250B2 (en) Sustained release formulations of oxymorphone
EP0700284B1 (fr) Formulations d'oxybutynine a liberation regulee
CA2285266C (fr) Formulations a liberation prolongee de derives d'erythromycine
AU2002320309A1 (en) Oxymorphone controlled release formulations
WO1996012477A1 (fr) Systeme d'administration orale a liberation lente contenant de l'oxybutynine
ZA200501541B (en) Bicifadine formulation
KR20130010509A (ko) 활성제 로딩된 과립과 추가의 활성제와의 조합물
US20090124650A1 (en) Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instructions on Effects of Alcohol
JP5226732B2 (ja) 催眠用圧縮成型製剤
HU225779B1 (en) Pharmaceutical composition containing paracetamol and drotaverine and process for producing it
ZA200301807B (en) Oxymorphone controlled release formulations.
US20100152269A1 (en) Modified-release formulations of azabicyclo derivatives

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AM AU BG BR BY CA CN CZ EE FI GE HU JP KG KP KR KZ LT LV NO NZ PL RO RU SI SK TJ UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase