EP1143936A2 - ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN $g(a)-AGONISTEN - Google Patents

ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN $g(a)-AGONISTEN

Info

Publication number
EP1143936A2
EP1143936A2 EP00901108A EP00901108A EP1143936A2 EP 1143936 A2 EP1143936 A2 EP 1143936A2 EP 00901108 A EP00901108 A EP 00901108A EP 00901108 A EP00901108 A EP 00901108A EP 1143936 A2 EP1143936 A2 EP 1143936A2
Authority
EP
European Patent Office
Prior art keywords
formulation according
pharmaceutical formulation
opioid
cellulose
release
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP00901108A
Other languages
German (de)
English (en)
French (fr)
Inventor
Johannes Bartholomäus
Jürgen Betzing
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gruenenthal GmbH
Original Assignee
Gruenenthal GmbH
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 Gruenenthal GmbH filed Critical Gruenenthal GmbH
Publication of EP1143936A2 publication Critical patent/EP1143936A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/485Morphinan derivatives, e.g. morphine, codeine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules 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
    • A61K9/5084Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect

Definitions

  • the invention relates to pharmaceutical formulations containing an opioid, an ⁇ -agonist and / or in each case its physiologically tolerable salt, from which at least one drug active ingredient is released with a delay.
  • opioids are used to relieve medium-weight and severe acute pain.
  • a major disadvantage of using opioids is the strong side effects associated with them. So side effects often occur on the gastrointestinal tract, such. B. constipation. Respiratory depression also arises as well as with repeated administration a dependency that can lead to abuse. Another disadvantage is the rapid development of tolerance.
  • opioids and ⁇ -agonists as monopreparations using various pharmaceutical formulations is known.
  • retard systems with opioids as described in WO95 / 14460 or EP-A-0 647 448, in which butyrates, ketobemidones, codeins and the like are also used, among others.
  • EP-B-0 271 193 discloses a retard system that uses only hydromorphone.
  • Retardation systems with ⁇ -agonists are disclosed in EP-A-0 805 677 or US 5,484,607. In both cases, only clonidine is used as the ⁇ -agonist.
  • the object of the present invention was therefore to provide a pharmaceutical formulation which is suitable for the treatment of severe to very severe pain, which does not have the typical side effects of the opioids, and which in particular delays the development of an opioid tolerance for a very long time or completely prevents it .
  • this object is achieved by the provision of pharmaceutical formulations which contain an opioid, an ⁇ -agonist and / or in each case its physiologically compatible salt, from which at least one active pharmaceutical ingredient is released with a delay.
  • the opioid is preferably released with a delay from the pharmaceutical formulation according to the invention.
  • the delayed release of the opioid preferably takes place over a period of 8 hours, especially during preferably 12 hours and very particularly preferably over 24 hours.
  • Both pharmaceutical active ingredients are also preferably released with a delay from the pharmaceutical formulation according to the invention.
  • the pharmaceutical formulation according to the invention preferably contains morphine, hydromorphone, codeine, oxycodone, dihydrocodeine, dextropropoxyphene, buprenorphine, levomethadone, fentanyl, sufentanil, etorphin, pentazocin, tilidine, tramadol, levorphanol, methadone and piridone or piridone, dihydromine or dihydromine as opioid physiologically acceptable salt of the opioids mentioned.
  • the pharmaceutical formulation according to the invention particularly preferably contains morphine, tramadol and / or a physiologically tolerable salt thereof as opioids.
  • the pharmaceutical formulation according to the invention preferably contains, as ⁇ -agonists, clonidine, guanfacin, guanabenz, lofexidine, adrenaline, methyldopa, noradrenaline, methoxamine, oxymetazoline, xylometazoline, teryzoline, ST-91, medetomidine, dexmedetomidine, agmatine, UK 14,304-paronidine U-47,476A, DJ-741, ICI-106270, xylazine, talipexol (BHT-920), naphazoline, tizanidine and / or a physiologically acceptable salt of the said ⁇ -agonists.
  • ⁇ -agonists clonidine, guanfacin, guanabenz, lofexidine, adrenaline, methyldopa, noradrenaline, methoxamine, oxymetazoline, xylometazoline, tery
  • the pharmaceutical formulation according to the invention particularly preferably contains clonidine, guanfacin and / or a physiologically tolerable salt thereof as ⁇ -agonists.
  • the pharmaceutical formulation according to the invention very particularly preferably contains morphine and / or tramadol as the opioid and clonidine and / or its physiologically tolerable salt in each case as the ⁇ -agonist.
  • Acetates, tatrates, sulfates, hydrochlorides, phosphates and additionally salicylates and acetylsalicylates for the group of opioids are preferably used as physiologically compatible salts of the active ingredients.
  • the weight ratio of the opioid to the ⁇ -agonist in the pharmaceutical formulations according to the invention is preferably 200 to 1 to 10 to 1. In a particularly preferred embodiment, the weight ratio of the opioid to the ⁇ -agonist is 100 to 1 to 10 to 1.
  • the pharmaceutical formulation according to the invention is preferably administered orally.
  • Preferred oral medicament formulations are tablets, dragees or capsules, particularly preferably tablets, very particularly preferably multilayer tablets.
  • the pharmaceutical formulation according to the invention can also be present in multiparticulate form, such as, for. B. in the form of microtables, microcapsules, ion exchangers, granules, active ingredient crystals or pellets.
  • the pharmaceutical formulation according to the invention can preferably also be in the form of a pellet tablet, which particularly preferably disintegrates quickly.
  • the respective active ingredients can be retarded preferably by means of a retarding coating, fixation to an ion exchange resin, embedding in a retarding matrix or a combination thereof.
  • Suitable sustained release coatings preferably include water-insoluble waxes or polymers such as acrylic resins Poly (meth) acrylates, or water-insoluble celluloses, preferably ethyl cellulose. These materials are known from the prior art, for example Bauer, Lehmann, Osterwald, Rothgang “Coated Pharmaceutical Formulas,ticianliche Verlagsgesellschaft mbH Stuttgart, 1988, page 69 ff. They are hereby introduced as a reference.
  • the sustained release coatings can also be non-retarding, preferably water-soluble polymers in amounts of up to 30% by weight, such as polyvinylpyrrolidone or water-soluble celluloses, preferably hydroxypropylmethyl cellulose or hydroxypropyl cellulose, and / or hydrophilic pore formers , such as sucrose, sodium chloride or mannitol and / or the known plasticizers.
  • Colestyramine is preferably used as the anionic ion exchange resin
  • polystyrene sulfonates are preferably used as the cationic ion exchange resins.
  • the active ingredients can also be present in a retarding matrix, preferably evenly distributed therein.
  • hydrophilic materials which are known to the person skilled in the art can be used as matrix materials.
  • Polymers particularly preferably cellulose ethers, cellulose esters and / or acrylic resins, are preferably used as the hydrophilic matrix materials.
  • Particularly preferred matrix materials are ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, poly (meth) acrylic acid and / or their derivatives, such as their salts, amides or esters.
  • Matrix materials made of hydrophobic materials such as hydrophobic polymers, waxes, fats, long-chain fatty acids, fatty alcohols or corresponding esters or ethers or mixtures thereof, are likewise preferred.
  • Mono- or diglycerides of C12-C30 fatty acids and / or C12-C30 fatty alcohols and / or waxes or mixtures thereof are particularly preferably used as hydrophobic materials.
  • sustained-release pharmaceutical formulations can also contain both active ingredients in a delayed form.
  • the pharmaceutical formulation according to the invention can also contain at least one of the active ingredients in addition to its retarded form in the non-retarded form. By combining it with the immediately released active ingredient, a high initial dose can be achieved for quick pain relief. The slow release from the retarded form then prevents the analgesic effect from subsiding. It is particularly preferred to set the release of the active ingredients in such a way that the sustained-release pharmaceutical formulation has to be administered at most twice, preferably only once a day. Because of the effect of the analgesics, the person skilled in the art knows in which mixing ratios they are to be used so that the desired release of the active compounds is achieved.
  • the pharmaceutical formulations according to the invention can have further coatings. Coatings that dissolve depending on the pH can also be present as coatings. In this way it can be achieved that the subunits pass through the gastrointestinal tract unresolved and are only released in the intestinal tract. Coatings can also be used to improve the taste.
  • the pharmaceutical formulations according to the invention can be prepared by the various methods known to the person skilled in the art, for example Tablets are produced by the customary processes, such as, for example, by extrusion, build-up processes, wet granulation, fluidized bed processes, dry mixtures or pressing processes. If the pharmaceutical formulation according to the invention, e.g. the tablet has coatings, these can be made using conventional methods, e.g. Drying, spraying on solutions, dispersions or suspensions, by melt processes or by powder application processes.
  • the amount of active ingredient to be administered depends on the active ingredients to be used and on the route of administration.
  • clonidine is particularly preferably in an amount between 1 ⁇ g and 500 ⁇ g, particularly preferably between 10 ⁇ g and 50 ⁇ g, in each case based on the base, and guanfacin preferably in an amount between 5 ⁇ g and 900 ⁇ g between 100 ⁇ g and 500 ⁇ g, based in each case on the base.
  • morphine is preferably used in an amount between 0.1 mg and 20 mg, particularly preferably in an amount between 0.5 mg and 5 mg, in each case based on the base, and tramadol preferably in an amount between 1 mg and 50 mg, particularly preferably in an amount between 1 mg and 20 mg, based in each case on the base.
  • the pharmaceutical formulations according to the invention are preferably administered orally, parenterally or transdermally, particularly preferably orally.
  • Transdermal slow release formulations can e.g. B. in the form of plasters with one or more drug matrices or one or more drug depots and a control membrane.
  • the pharmaceutical formulations according to the invention can contain, in addition to an opioid, an ⁇ -agonist and / or in each case its physiologically compatible salt, further active pharmaceutical ingredients and / or auxiliaries.
  • the pharmaceutical auxiliaries are preferably binders, fillers, lubricants, carrier materials, disintegrants, solvents, diluents, dyes, retarding auxiliaries and / or mixtures thereof.
  • the choice of excipients and the megnen to be used depend on whether the slow-release medicinal forms according to the invention are used orally, parenterally or transdermally.
  • fillers is understood to mean, inter alia, starch, microcrystalline cellulose, dextrose, mannitol or mixtures thereof.
  • Hydroxypropyl methyl celluloses polyvinyl pyrrolidines, hydroxypropyl celluloses, starch paste or mixtures thereof can preferably be used as binders.
  • Low-substituted hydroxypropyl celluloses crosspovidones, Crosscarmellose, starches, pectins, alginates, surfactants or mixtures thereof are used.
  • Magnesium tearat, stearic acid, calcium stearate, fatty alcohols or mixtures thereof are examples of the group of the lubricants that are used.
  • Another object of the present invention is. also the use of the pharmaceutical formulations according to the invention for combating moderate to very severe pain.
  • the pharmaceutical formulations according to the invention show a marked increase in the analgesic effect. This means that with the same analgesic effect, the amount of opioid used can be significantly reduced. In addition, the dependency potential caused by opioids and the constipating effect compared to the sole use of an opioid are significantly reduced.
  • a particular advantage of the slow-release pharmaceutical formulations according to the invention is that the development of a tolerance to the opioid is very much delayed or completely avoided.
  • the following examples serve to explain the invention, but do not restrict the general idea of the invention.
  • the granulation was carried out in a Lödiger high-speed mixer FM 5 and the tablets were produced with a fat eccentric press.
  • PVP polyvinylpyrrolidones
  • morphine HCl in the context of the present invention means morphine HCl trihydrate.
  • tramadol HCl means tramadol HCl trihydrate.
  • RPM revolutions per minute
  • the two-layer tablet produced consisted of a retarded layer containing the active ingredient morphine HCl and an unretarded layer containing the active ingredient clonidine.
  • Morphine HCl, part of the lactose, hydroxyethyl cellulose and cetostearyl alcohol were processed in a suitable mixer for the retarded granules. The mixture was heated to 80 ° C and granulated. After cooling, the granules were sieved and mixed with magnesium stearate and talc.
  • the remaining lactose and corn starch were granulated with a solution of clonidine HCl, PVP 30 and purified water in a suitable mixer. Magnesium stearate and PVP Cl were added to the dried granulate. The two granules were pressed into two-layer tablets.
  • the two-layer tablets produced consisted of a retarded layer containing the active ingredient morphine HCl and an unretarded layer containing the active ingredient clonidine.
  • Morphine HCl part of the lactose, hydroxethyl cellulose and cetostearyl were used for the retarded granules.
  • alcohol processed in a suitable mixer. The mixture was heated to 80 ° C and granulated. After cooling, the granules were sieved and mixed with magnesium stearate and talc.
  • the remaining lactose and corn starch were granulated with a solution of clonidine HCl, PVP 30 and purified water in a suitable mixer. Magnesium stearate and PVP Cl were added to the dried granulate. The two granules were pressed into two-layer tablets.
  • the two-layer tablets produced consisted of a delayed-release layer with the active ingredient Tramadol HCl and a further delayed-release layer which contained the active ingredient clonidine HCL.
  • Tramadol HCl was mixed with microcrystalline cellulose, methyl hydroxypropyl cellulose, part of the highly disperse silicon dioxide and magnesium stearate and pressed into tablets. After that, the tab Lithuanian sifted, mixed with the remaining magnesium stearate and highly disperse silicon dioxide.
  • Lactose and hydroxyethyl cellulose were placed in a suitable mixer and mixed.
  • the mixture was moistened with a solution of clonidine HCl in water. After drying, the mixture was mixed with cetostearyl alcohol, heated to 80 ° C. and then granulated. The cooled granules were sieved and mixed with talc and magnesium stearate and the two granules were compressed into two-layer tablets.
  • the two-layer tablets produced consisted of a delayed-release layer with the active ingredient Tramadol HCl and a further delayed-release layer which contained the active ingredient clonidine HCL.
  • HCl was mixed with microcrystalline cellulose, methylhydroxypropyl cellulose, part of the highly disperse silicon dioxide and magnesium stearate and pressed into tablets. After that, the tablets were broken screened, mixed with the remaining magnesium stearate and the highly disperse silicon dioxide.
  • Lactose and hydroxyethyl cellulose were placed in a suitable mixer and mixed. The mixture was moistened with an aqueous solution of clonidine HCl. After drying, it was mixed with cetostearyl cellulose, heated to 80 ° C. and then granulated. The cooled granules were sieved and mixed with talc and magnesium stearate and the two granules pressed into two-layer tablets.
  • the active ingredient clonidine was applied to slow-release morphine pellets as an ⁇ -agonist using a suitable coating system.
  • the pellets produced were filled into capsules or pressed into tablets.
  • the components of the delayed pellets contained:
  • Neutral starter cores were placed in a paint shop and moistened with an ethanolic polyethylene glycol 4000 solution. A mixture of morphine sulfate and lactose was applied several times to the wet cores and the cores were dried. This process was repeated until the morphine sulfate / lactose mixture was completely applied.
  • the total amount per capsule was 31.98 mg.
  • Microcrystalline cellulose and low-substituted hydroxypropyl cellulose were moistened with an aqueous solution of hydroxypropyl methyl cellulose and clonidine HCl.
  • the mixture was extruded through a 0.5 mm perforated disk with a Pharmatex 35 T extruder, rounded in a Spheromat and dried in the fluidized bed.
  • the coated tramadol and clonidine pellets were filled into capsules and compressed into tablets.
  • the matrix tablet contained the following composition
  • Morphine HCl, lactose, hydroxyethyl cellulose and cetostearyl alcohol were mixed.
  • the mixture was moistened with aqueous clonidine HCl.
  • the resulting mixture was dried, then heated to 80 ° C. and granulated. After cooling, the granules were sieved, mixed with magnesium stearate and tableted.
  • the total amount of starting materials was 200 g.
  • the components were sieved (0.63 mm), then mixed in a small cube mixer for 10 minutes and compressed on a Korsch EK 0 eccentric tablet press to tablets of 10 mm diameter with a radius of curvature of 8.5 mm and an average weight of 300 mg .

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP00901108A 1999-01-18 2000-01-17 ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN $g(a)-AGONISTEN Withdrawn EP1143936A2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19901684 1999-01-18
DE19901684 1999-01-18
PCT/EP2000/000318 WO2000041681A2 (de) 1999-01-18 2000-01-17 ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN α-AGONISTEN

Publications (1)

Publication Number Publication Date
EP1143936A2 true EP1143936A2 (de) 2001-10-17

Family

ID=7894563

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00901108A Withdrawn EP1143936A2 (de) 1999-01-18 2000-01-17 ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN $g(a)-AGONISTEN

Country Status (15)

Country Link
US (1) US20020044966A1 (es)
EP (1) EP1143936A2 (es)
JP (1) JP2002534458A (es)
AR (1) AR022252A1 (es)
AU (1) AU772886B2 (es)
BR (1) BR0000578A (es)
CA (1) CA2359273A1 (es)
CO (1) CO5160243A1 (es)
HU (2) HUP0105043A3 (es)
NO (2) NO20000225D0 (es)
NZ (1) NZ513501A (es)
PE (1) PE20001396A1 (es)
SK (1) SK10012001A3 (es)
UY (1) UY25936A1 (es)
WO (1) WO2000041681A2 (es)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2374717T3 (es) 1999-10-29 2012-02-21 Euro-Celtique S.A. Formulaciones de hidrocodona de liberación controlada.
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
CA2424021A1 (en) * 2000-09-29 2002-04-04 Board Of Trustees Operating Michigan State University Catecholamine compositions and uses thereof
KR100960200B1 (ko) 2000-10-30 2010-05-27 유로-셀티크 소시에떼 아노뉨 서방성 하이드로코돈 제형
US6287599B1 (en) * 2000-12-20 2001-09-11 Shire Laboratories, Inc. Sustained release pharmaceutical dosage forms with minimized pH dependent dissolution profiles
EP1395243A2 (en) * 2001-05-31 2004-03-10 SkyePharma Inc. Encapsulation of nanosuspensions in liposomes and microspheres
US8329216B2 (en) * 2001-07-06 2012-12-11 Endo Pharmaceuticals Inc. Oxymorphone controlled release formulations
KR20030034171A (ko) * 2001-07-06 2003-05-01 엔도 파마슈티걸즈, 인크. 옥시모르폰 제어 방출 제형
DE10141650C1 (de) 2001-08-24 2002-11-28 Lohmann Therapie Syst Lts Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen
AU2002337686B2 (en) * 2001-09-26 2008-05-15 Penwest Pharmaceuticals Company Opioid formulations having reduced potential for abuse
US7854230B2 (en) * 2001-10-22 2010-12-21 O.R. Solutions, Inc. Heated medical instrument stand with surgical drape and method of detecting fluid and leaks in the stand tray
US8487002B2 (en) * 2002-10-25 2013-07-16 Paladin Labs Inc. Controlled-release compositions
TWI319713B (en) * 2002-10-25 2010-01-21 Sustained-release tramadol formulations with 24-hour efficacy
US7648981B2 (en) * 2003-02-28 2010-01-19 Ym Biosciences Inc. Opioid delivery system
US7648982B2 (en) * 2003-02-28 2010-01-19 Ym Biosciences Inc. Opioid delivery system
US20060172006A1 (en) * 2003-10-10 2006-08-03 Vincent Lenaerts Sustained-release tramadol formulations with 24-hour clinical efficacy
US20050100594A1 (en) * 2003-11-12 2005-05-12 Nilendu Sen Pharmaceutical formulation containing muscle relaxant and COX-II inhibitor
DE102005013726A1 (de) * 2005-03-22 2006-09-28 Grünenthal GmbH Transdermale therapeutische Systeme mit verbesserter Verträglichkeit
US7485323B2 (en) * 2005-05-31 2009-02-03 Gelita Ag Process for making a low molecular weight gelatine hydrolysate and gelatine hydrolysate compositions
NZ565649A (en) * 2005-07-28 2011-03-31 Shire Llc Pharmaceutical formulations/composition of guanfacine suitable for single dose form administration daily
JP5269595B2 (ja) 2005-09-09 2013-08-21 アンジェリーニ ラボファーム リミテッド ライアビリティ カンパニー 1日1回投与用トラゾドン組成物
US20070212414A1 (en) * 2006-03-08 2007-09-13 Penwest Pharmaceuticals Co. Ethanol-resistant sustained release formulations
US20080069891A1 (en) * 2006-09-15 2008-03-20 Cima Labs, Inc. Abuse resistant drug formulation
US8445018B2 (en) 2006-09-15 2013-05-21 Cima Labs Inc. Abuse resistant drug formulation
US20100172991A1 (en) * 2007-06-08 2010-07-08 Henry Joseph Horacek Extended Release Formulation and Methods of Treating Adrenergic Dysregulation
US20090087490A1 (en) 2007-06-08 2009-04-02 Addrenex Pharmaceuticals, Inc. Extended release formulation and method of treating adrenergic dysregulation
US20090124650A1 (en) * 2007-06-21 2009-05-14 Endo Pharmaceuticals, Inc. Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instructions on Effects of Alcohol
WO2009130715A1 (en) * 2008-04-25 2009-10-29 Cadila Healtcare Limited Rapidly disintegrating oral compositions of tramadol
EP2309993A1 (en) * 2008-06-25 2011-04-20 US Worldmeds LLC Skin patches and sustained-release formulations comprising lofexidine for transdermal and oral delivery
US8603497B2 (en) * 2008-10-30 2013-12-10 National University Corporation Okayama University Composition for local anesthesia
NZ600640A (en) * 2009-12-17 2014-11-28 Cima Labs Inc Abuse-resistant formulations
EP2568977A1 (en) 2010-05-11 2013-03-20 Cima Labs Inc. Alcohol-resistant metoprolol-containing extended- release oral dosage forms
SG10201510564PA (en) 2010-12-22 2016-01-28 Purdue Pharma Lp Encased tamper resistant controlled release dosage forms
CA2850964C (en) 2011-10-05 2021-02-02 Jennifer L. Sanders Methods and compositions for treating foot or hand pain
US20130096170A1 (en) 2011-10-14 2013-04-18 Hospira, Inc. Methods of treating pediatric patients using dexmedetomidine
US8242158B1 (en) 2012-01-04 2012-08-14 Hospira, Inc. Dexmedetomidine premix formulation
EP3054935B1 (en) 2013-10-07 2020-12-09 Teikoku Pharma USA, Inc. Methods and compositions for treating attention deficit hyperactivity disorder, anxiety and insomnia using dexmedetomidine transdermal compositions
RU2646512C2 (ru) 2013-10-07 2018-03-05 ТЕЙКОКУ ФАРМА ЮЭсЭй, ИНК. Устройства для трансдермальной доставки дексмедетомидина и способы их применения
RU2648449C2 (ru) 2013-10-07 2018-03-26 ТЕЙКОКУ ФАРМА ЮЭсЭй, ИНК. Способы и композиции для трансдермальной доставки неседативного количества дексмедетомидина
US20150118300A1 (en) 2013-10-31 2015-04-30 Cima Labs Inc. Immediate Release Abuse-Deterrent Granulated Dosage Forms
EP3965733A4 (en) 2019-05-07 2023-01-11 Clexio Biosciences Ltd. ABUSE DETERRENT DOSAGE FORMS CONTAINING ESKETAMINE
US20220062200A1 (en) 2019-05-07 2022-03-03 Clexio Biosciences Ltd. Abuse-deterrent dosage forms containing esketamine
CN112494486B (zh) * 2020-12-07 2022-01-21 深圳善康医疗健康产业有限公司 一种用于减轻或消除阿片戒断综合症的药物组合物及应用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4946848A (en) * 1985-10-29 1990-08-07 Baker Cumins Dermatologicals, Inc. Method of treating pruritus with nalmefene and clonidine
PT99629A (pt) * 1991-11-28 1993-05-31 Antonio Feria Reis Valle Metodo de desintoxicacao de opiaceos
US5635204A (en) * 1994-03-04 1997-06-03 Montefiore Medical Center Method for transdermal induction of anesthesia, analgesia or sedation
DE19758564A1 (de) * 1997-11-11 1999-08-26 Gruenenthal Gmbh Formulierung einer Kombination aus Morphin und einem alpha¶2¶-adrenergem Agonisten und deren Verwendung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0041681A2 *

Also Published As

Publication number Publication date
US20020044966A1 (en) 2002-04-18
BR0000578A (pt) 2001-08-14
AU2109000A (en) 2000-08-01
JP2002534458A (ja) 2002-10-15
UY25936A1 (es) 2001-07-31
WO2000041681A3 (de) 2000-12-07
NO20013302D0 (no) 2001-07-03
PE20001396A1 (es) 2000-12-23
WO2000041681A2 (de) 2000-07-20
NO20000225D0 (no) 2000-01-17
AR022252A1 (es) 2002-09-04
CO5160243A1 (es) 2002-05-30
HUP0105043A2 (en) 2002-06-29
HUP0105043A3 (en) 2005-06-28
HU0000139D0 (en) 2000-03-28
NO20013302L (no) 2001-07-03
SK10012001A3 (sk) 2002-01-07
AU772886B2 (en) 2004-05-13
CA2359273A1 (en) 2000-07-20
NZ513501A (en) 2003-11-28

Similar Documents

Publication Publication Date Title
EP1143936A2 (de) ARZNEIFORMULIERUNGEN ENTHALTEND EIN OPIOID UND EINEN $g(a)-AGONISTEN
DE69214802T2 (de) Oxycodon-zusammensetzungen mit kontrollierter freisetzung
EP1020185B1 (de) Opioide Analgetika mit kontrollierter Wirkstofffreisetzung
EP1183015B1 (de) Mehrschichttablette zur verabreichung einer fixen kombination von tramadol und diclofenac
DE69429826T2 (de) Opioid-formulierungen zur schmerzbehandlung
DE60319252T2 (de) Formulierung von acetaminophen und tramadol mit verzögerter freisetzung
EP0642788B1 (de) Tramadolsalz enthaltende Arzneimittel mit verzögerter Wirkstofffreitsetzung
EP1207867A1 (de) Retardierte, orale, pharmazeutische darreichnungsformen
EP1289528A1 (de) Wirkstoffkombination enthaltend ein opioid mit fentanyl-artiger struktur und ketamin
EP1140031B1 (de) Kontrolliert freisetzende pharmazeutische zusammensetzung mit tilidinmesylat als wirkstoff
DE19901683B4 (de) Analgetikum mit kontrollierter Wirkstofffreisetzung
AT4589U2 (de) Oxycodon-zusammensetzung mit kontrollierter freisetzung
DE10215131A1 (de) Matrix zur verzögerten, gleichbleibenden und unabhängigen Freisetzung von Wirkstoffen
EP1928441A2 (de) Retardformulierung von 3-(2-dimethylaminomethyl-cyclohexyl)-phenol
WO2010105824A1 (de) Retigabin-tabletten, bevorzugt mit modifizierter freisetzung
DE102021119130A1 (de) Ethylcellulose-beschichtete Partikel enthaltend ein Salz aus Tapentadol und Phosphorsäure
WO2000066088A1 (de) Metamizol enthaltende, kontrolliert freisetzende pharmazeutische zusammensetzung
EP1289529A1 (de) Wirkstoffkombination enthaltend eine verbindung mit opioider wirksamkeit und eine weitere verbindung der formel i
EP1374859A1 (de) Feste pharmazeutische Zusammensetzung enthaltend Tilidinhydrochlorid
DE202014104573U1 (de) Pharmazeutische Zusammensetzung zur Schmerzbehandlung
WO2018087109A1 (de) Multipartikuläre arzneiform mit kontrollierter freisetzung von metamizol
MXPA01006899A (es) Formulaciones medicinales que contienen un opioide y un alfa antagonista

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010626

AK Designated contracting states

Kind code of ref document: A2

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

AX Request for extension of the european patent

Free format text: AL;LT PAYMENT 20010626;LV PAYMENT 20010626;MK;RO;SI PAYMENT 20010626

17Q First examination report despatched

Effective date: 20040302

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040713