JP2000510487A - 安定化された徐放性トラマドール製剤 - Google Patents
安定化された徐放性トラマドール製剤Info
- Publication number
- JP2000510487A JP2000510487A JP11507477A JP50747799A JP2000510487A JP 2000510487 A JP2000510487 A JP 2000510487A JP 11507477 A JP11507477 A JP 11507477A JP 50747799 A JP50747799 A JP 50747799A JP 2000510487 A JP2000510487 A JP 2000510487A
- Authority
- JP
- Japan
- Prior art keywords
- tramadol
- dosage form
- solid dosage
- matrix
- granules
- 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.)
- Granted
Links
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- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- HPNSNYBUADCFDR-UHFFFAOYSA-N chromafenozide Chemical compound CC1=CC(C)=CC(C(=O)N(NC(=O)C=2C(=C3CCCOC3=CC=2)C)C(C)(C)C)=C1 HPNSNYBUADCFDR-UHFFFAOYSA-N 0.000 description 1
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- 238000005520 cutting process Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical class CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
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- 238000003255 drug test Methods 0.000 description 1
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- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
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- 229940127022 high-dose drug Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- LDHBWEYLDHLIBQ-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide;hydrate Chemical compound O.[OH-].[O-2].[Fe+3] LDHBWEYLDHLIBQ-UHFFFAOYSA-M 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- XRCRWCVBMHENNE-UHFFFAOYSA-N sym-di-n-butyl citrate Natural products CCCCOC(=O)CC(O)(C(O)=O)CC(=O)OCCCC XRCRWCVBMHENNE-UHFFFAOYSA-N 0.000 description 1
- 229940051166 synthetic yellow iron oxide Drugs 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229960005196 titanium dioxide Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000723 toxicological property Toxicity 0.000 description 1
- 229960003107 tramadol hydrochloride Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940054370 ultram Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.トラマドールを活性薬剤として含有する安定化された徐放性経口固形投薬剤 であって、 マトリックスの調製時に溶融または軟化させたワックス様物質を含有する疎 水性物質のマトリックス中に分散された有効量のトラマドールまたは製薬上許容 されるその塩を含み、 該固形投薬剤が安定な溶解プロフィルを呈する最終点に到達するように、十 分な時間をかけて約35℃〜約65℃の温度で硬化され、 該最終点が、硬化直後の該固形投薬剤の溶解プロフィルを、40℃、相対湿度 75%の促進保存条件下に少なくとも1ヶ月暴露した後で得られる該固形投薬剤の 溶解プロフィルと比較することによって決定される、安定化された徐放性経口固 形投薬剤。 2.前記硬化が約40℃〜約60℃の温度において約4〜約72時間かけて行われる請 求項1記載の安定化された徐放性経口固形投薬剤。 3.前記硬化が約45℃〜約55℃の温度において約4〜約72時間かけて行われる請 求項1記載の安定化された徐放性経口固形投薬剤。 4.前記硬化が約24時間かけて行われる請求項1〜3のいずれか1項に記載の安 定化された徐放性経口固形投薬剤。 5.前記ワックス様物質が、水素化植物油、水素化ヒマシ油、パラフィン、高級 脂肪族アルコール、高級脂肪族酸、長鎖脂肪酸、脂肪酸エステル、およびこれら の混合物からなる群より選ばれる請求項1〜4のいずれか1項に記載の安定化さ れた徐放性経口固形投薬剤。 6.前記疎水性物質が、アクリル系ポリマー、アルキルセルロース、およびこれ らの混合物からなる群より選ばれる疎水性ポリマーを更に含有する請求項1〜5 のいずれか1項に記載の安定化された徐放性経口固形投薬剤。 7.親水性ポリマーを更に含有する請求項1〜6のいずれか1項に記載の安定化 された徐放性経口固形投薬剤。 8.前記親水性ポリマーがセルロースエーテルである請求項1〜7のいずれか1 項 に記載の安定化された徐放性経口固形投薬剤。 9.前記マトリックスが、トラマドール、高級脂肪族アルコール、ならびにアク リル系ポリマー、アルキルセルロースおよびこれらの混合物からなる群より選 ばれる疎水性ポリマーを含有する請求項1〜4のいずれか1項に記載の安定化 された徐放性経口固形投薬剤。 10.前記マトリックスがトラマドールおよび水素化植物油を含有する請求項1 〜4のいずれか1項に記載の安定化された徐放性経口固形投薬剤。 11.錠剤である請求項1〜10のいずれか1項に記載の安定化された徐放性経 口固形投薬剤。 12.前記促進保存条件下に暴露する前に行われるin-vitro溶解と比較した場合 、任意の所定の溶解時間点において該溶解時間点におけるトラマドールの全放出 量の約20%を超える変動を示さない量でトラマドールを放出する請求項1〜11 のいずれか1項に記載の安定化された徐放性経口固形投薬剤。 13.前記疎水性ポリマーが前記疎水性物質の約0重量%〜約80重量%を占める請 求項6記載の安定化された徐放性経口固形投薬剤。 14.前記疎水性ポリマーが前記疎水性物質の約30重量%〜約50重量%を占める請 求項6記載の安定化された徐放性経口固形投薬剤。 15.トラマドールを活性薬剤として含有する安定化された徐放性経口固形投薬 剤を調製する方法であって、 マトリックスの調製時に溶融または軟化されるワックス様物質を含有する疎 水性物質のマトリックス中に分散されたトラマドールまたは製薬上許容されるそ の塩を含んでなるマトリックスを調製する工程、および、 その後で、該マトリックスが安定な溶解プロフィルを呈する最終点に達する ように、十分な時間をかけて約35℃〜約65℃の温度で該マトリックスを硬化させ る工程(該最終点は、硬化直後の該マトリックスの溶解プロフィルを、40℃、相 対湿度75%の促進保存条件下に少なくとも1ヶ月暴露した後で得られる該マトリ ックスの溶解プロフィルと比較することによって決定される)、 を含む前記方法。 16.前記マトリックスを圧縮して錠剤にする工程を更に含む請求項15記載の 方 法。 17.前記錠剤が、 前記ワックス様物質を軟化または溶融するのに十分な高温で、前記トラマド ールおよび前記疎水性物質を、場合により更に医薬用賦形剤と一緒に押出機中に 供給する工程、 該混合物を押出する工程、 該混合物を造粒する工程、 得られた顆粒を平滑化する工程、および、 該顆粒を圧縮して錠剤にする工程 により調製される請求項16記載の方法。 18.前記錠剤が、 疎水性ポリマー分散体を、流動床ドライヤー中でトラマドールと不活性希釈 剤との混合物上に噴霧して、顆粒を得る工程、 溶融されたワックス様物質を高剪断ミキサー中で顆粒中に混合する工程、 該混合物をスクリーンに通してタルクと混合する工程、 得られた物質を平滑化する工程、および、 平滑化された該顆粒を圧縮して錠剤にする工程 により調製される請求項16記載の方法。 19.前記錠剤が、 溶融されたワックス様物質を製薬上好適なミキサー中でトラマドール上に注 ぐ工程、 該混合物を固化および冷却する工程、 その後で、該混合物を粉砕する工程、 該混合物を平滑化する工程、および、 平滑化された該顆粒を圧縮して錠剤にする工程 により調製される請求項16記載の方法。 20.前記錠剤が、 ワックス様物質を溶融および造粒する工程、 セルロースエーテルを水和し、それを造粒する工程、 トラマドールを、造粒された該溶融体、造粒された該セルロースエーテル、 またはこれらの混合物のうちのいずれかとブレンドする工程、 得られた顆粒を乾燥させる工程、および、 その後で、場合により、適切な量の不活性な製薬上許容される希釈剤と混合 し、この混合物を圧縮して錠剤にする工程 により調製される請求項16記載の方法。 21.前記疎水性物質が前記ワックス様物質のほかに親水性または疎水性のポリ マーを含有し、 前記錠剤が、 (a) 前記トラマドールを用いてまたは用いずに、該疎水性または親水性のポ リマーおよび場合により希釈剤を湿式造粒する工程、 (b) 得られた顆粒の乾燥および分粒を行う工程、 (c) 工程(a)で組合せが済んでいない場合に前記トラマドールを該顆粒と組 み合わせ、好適なミキサーを用いて該顆粒中に溶融状態の前記ワックス様物質を 導入する工程、 (d) 該顆粒の冷却および分粒を行う工程、および (e) その後で、該顆粒を平滑化し、平滑化された該顆粒を圧縮して錠剤にする 工程 により調製される請求項16記載の方法。 22.前記硬化が約40℃〜約60℃の温度において約4〜約72時間かけて行われる 請求項15〜21のいずれか1項に記載の方法。 23.前記硬化が約45℃〜約55℃の温度において約4〜約72時間かけて行われる 請求項15〜21のいずれか1項に記載の方法。 24.前記硬化が約24時間かけて行われる請求項15〜21のいずれか1項に記 載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US5160297P | 1997-07-02 | 1997-07-02 | |
US60/051,602 | 1997-07-02 | ||
PCT/US1998/014087 WO1999001111A1 (en) | 1997-07-02 | 1998-07-02 | Stabilized sustained release tramadol formulations |
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JP2003140053A Division JP4576097B2 (ja) | 1997-07-02 | 2003-05-19 | 安定化された徐放性トラマドール製剤 |
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JP2000510487A true JP2000510487A (ja) | 2000-08-15 |
JP3739410B2 JP3739410B2 (ja) | 2006-01-25 |
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JP50747799A Expired - Lifetime JP3739410B2 (ja) | 1997-07-02 | 1998-07-02 | 安定化された徐放性トラマドール製剤 |
JP2003140053A Expired - Lifetime JP4576097B2 (ja) | 1997-07-02 | 2003-05-19 | 安定化された徐放性トラマドール製剤 |
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US (2) | US6306438B1 (ja) |
EP (1) | EP1009387B1 (ja) |
JP (2) | JP3739410B2 (ja) |
AT (1) | ATE322892T1 (ja) |
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Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Families Citing this family (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL109460A (en) | 1993-05-10 | 1998-03-10 | Euro Celtique Sa | Controlled release formulation comprising tramadol |
WO1999001111A1 (en) * | 1997-07-02 | 1999-01-14 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
US6375957B1 (en) | 1997-12-22 | 2002-04-23 | Euro-Celtique, S.A. | Opioid agonist/opioid antagonist/acetaminophen combinations |
PT2266564E (pt) | 1997-12-22 | 2013-06-20 | Euro Celtique Sa | Forma de dosagem farmacêutica por via oral compreendendo uma combinação de um agonista opióide e de um antagonista opióide |
DE19901683B4 (de) * | 1999-01-18 | 2005-07-21 | Grünenthal GmbH | Analgetikum mit kontrollierter Wirkstofffreisetzung |
CN1202815C (zh) * | 1999-08-31 | 2005-05-25 | 格吕伦塔尔有限公司 | 含有曲马朵糖精盐的持续释放给药剂型 |
BRPI0108380B8 (pt) | 2000-02-08 | 2021-05-25 | Euro Celtique S/A | fórmulas de opióides agonistas resistentes à adulteração, método para diminuir o abuso de um opióide agonista numa fórmula de dosagem oral, método de preparação de uma fórmula de dosagem oral e método de tratamento da dor |
WO2002092060A1 (en) | 2001-05-11 | 2002-11-21 | Endo Pharmaceuticals, Inc. | Abuse-resistant controlled-release opioid dosage form |
JP4310605B2 (ja) | 2001-05-25 | 2009-08-12 | 大塚製薬株式会社 | 医薬用組成物 |
US20030130297A1 (en) | 2001-07-06 | 2003-07-10 | Endo Pharmaceuticals, Inc. | Oral administration of 6-hydroxy-oxymorphone for use as an analgesic |
US8329216B2 (en) | 2001-07-06 | 2012-12-11 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
DK1416842T3 (da) | 2001-07-18 | 2009-03-16 | Euro Celtique Sa | Farmaceutiske kombinationer af oxycodon og naloxon |
US20030044458A1 (en) | 2001-08-06 | 2003-03-06 | Curtis Wright | Oral dosage form comprising a therapeutic agent and an adverse-effect agent |
ATE431738T1 (de) | 2001-08-06 | 2009-06-15 | Euro Celtique Sa | Opioid-agonist-formulierungen mit freisetzbarem und sequestriertem antagonist |
WO2003013433A2 (en) | 2001-08-06 | 2003-02-20 | Euro-Celtique S.A. | Sequestered antagonist formulations |
CA2508907A1 (en) * | 2001-11-08 | 2003-05-15 | Atrium Medical Corporation | Intraluminal device with a coating containing a therapeutic agent |
US20050182056A9 (en) * | 2002-02-21 | 2005-08-18 | Seth Pawan | Modified release formulations of at least one form of tramadol |
PT1476138E (pt) * | 2002-02-21 | 2012-02-14 | Valeant Internat Barbados Srl | Formulações de libertação modificada de pelo menos uma forma de tramadol |
US8323692B2 (en) | 2002-02-21 | 2012-12-04 | Valeant International Bermuda | Controlled release dosage forms |
US8128957B1 (en) | 2002-02-21 | 2012-03-06 | Valeant International (Barbados) Srl | Modified release compositions of at least one form of tramadol |
CA2479252A1 (en) * | 2002-03-22 | 2003-10-02 | Cilag Ag | Sustained release formulation of tramadol |
PT2425821T (pt) * | 2002-04-05 | 2017-08-23 | Mundipharma Farmacêutica Lda | Preparação farmacêutica contendo oxicodona e naloxona |
US7776314B2 (en) | 2002-06-17 | 2010-08-17 | Grunenthal Gmbh | Abuse-proofed dosage system |
US10004729B2 (en) | 2002-07-05 | 2018-06-26 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
AR040682A1 (es) | 2002-07-25 | 2005-04-13 | Pharmacia Corp | Forma de dosificacion una vez al dia de pramipexol |
CA2498798A1 (en) * | 2002-09-20 | 2004-04-01 | Alpharma, Inc. | Sustained-release opioid formulations and methods of use |
ES2677769T3 (es) | 2002-09-20 | 2018-08-06 | Alpharma Pharmaceuticals Llc | Subunidad secuestrante y composiciones y procedimientos relacionados |
CN1942175B (zh) * | 2002-10-25 | 2010-05-26 | 莱博法姆公司 | 24小时有效的曲马多缓释制剂 |
TWI319713B (en) | 2002-10-25 | 2010-01-21 | Sustained-release tramadol formulations with 24-hour efficacy | |
US8487002B2 (en) | 2002-10-25 | 2013-07-16 | Paladin Labs Inc. | Controlled-release compositions |
PT1558935E (pt) * | 2002-10-25 | 2008-10-16 | Labopharm Inc | Composições de libertação controlada |
DE10300325A1 (de) * | 2003-01-09 | 2004-07-22 | Hexal Ag | Granulat mit öliger Substanz, Herstellungsverfahren und Tablette |
EP1905435A3 (en) | 2003-03-11 | 2008-05-14 | Euro-Celtique S.A. | Titration dosing regimen for controlled release tramadol |
US7413749B2 (en) * | 2003-03-11 | 2008-08-19 | Purdue Pharma L.P. | Titration dosing regimen for controlled release tramadol |
US20040202717A1 (en) | 2003-04-08 | 2004-10-14 | Mehta Atul M. | Abuse-resistant oral dosage forms and method of use thereof |
TWI347201B (en) | 2003-04-21 | 2011-08-21 | Euro Celtique Sa | Pharmaceutical products,uses thereof and methods for preparing the same |
DE10336400A1 (de) | 2003-08-06 | 2005-03-24 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
DE102004032051A1 (de) | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform |
DE10361596A1 (de) | 2003-12-24 | 2005-09-29 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
US8075872B2 (en) | 2003-08-06 | 2011-12-13 | Gruenenthal Gmbh | Abuse-proofed dosage form |
US20070048228A1 (en) | 2003-08-06 | 2007-03-01 | Elisabeth Arkenau-Maric | Abuse-proofed dosage form |
NZ545202A (en) | 2003-08-06 | 2010-03-26 | Gruenenthal Chemie | Abuse-proofed dosage form comprising opiods and a high molecular weight polyethylene oxide |
DE102005005446A1 (de) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Bruchfeste Darreichungsformen mit retardierter Freisetzung |
EP1604666A1 (en) | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD) |
EP1604667A1 (en) * | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the restless leg syndrome |
WO2005123039A1 (en) | 2004-06-12 | 2005-12-29 | Collegium Pharmaceutical, Inc. | Abuse-deterrent drug formulations |
DE102004032049A1 (de) | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Gegen Missbrauch gesicherte, orale Darreichungsform |
EP1771159A4 (en) * | 2004-07-22 | 2009-04-29 | Amorepacific Corp | SLOW RELEASE PREPARATIONS CONTAINING TOPIRAMATE AND PROCESS FOR PRODUCING THE SAME |
CA2572864C (en) | 2004-08-13 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof |
US20060067976A1 (en) | 2004-09-28 | 2006-03-30 | Atrium Medical Corporation | Formation of barrier layer |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
DE102005005449A1 (de) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
EP1695700A1 (en) * | 2005-02-28 | 2006-08-30 | Euro-Celtique S.A. | Dosage form containing oxycodone and naloxone |
EP1702558A1 (en) | 2005-02-28 | 2006-09-20 | Euro-Celtique S.A. | Method and device for the assessment of bowel function |
US7884136B2 (en) | 2005-06-27 | 2011-02-08 | Biovail Laboratories International S.R.L. | Modified-release formulations of a bupropion salt |
RU2008104638A (ru) | 2005-07-07 | 2009-08-20 | Фарнэм Компаниз, Инк. (Us) | Фармацевтические композиции хорошо растворимых в воде лекарственных средств, обеспечивающих их замедленное высвобождение |
UA91376C2 (ru) * | 2005-08-24 | 2010-07-26 | Рубикон Рисеч Пвт Лтд. | Рецептура с контролируемым высвобождением |
DK1940467T3 (da) | 2005-09-09 | 2017-02-13 | Paladin Labs Inc | Lægemiddelsammensætning med langvarig frigivelse |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
GB2431875A (en) * | 2005-10-31 | 2007-05-09 | Alza Corp | Methods of reducing alcohol-induced dose dumping for opioid sustained release oral dosage forms |
CN1957909B (zh) * | 2005-10-31 | 2013-09-11 | 阿尔扎公司 | 降低鸦片样物质持续释放口服剂型的由醇诱导的剂量突然释放的方法 |
ES2904546T3 (es) | 2006-02-03 | 2022-04-05 | Opko Renal Llc | Tratamiento de la insuficiencia y deficiencia de vitamina D con 25-hidroxivitamina D2 y 25-hidroxivitamina D3 |
US20070190141A1 (en) * | 2006-02-16 | 2007-08-16 | Aaron Dely | Extended release opiate composition |
ES2385612T3 (es) | 2006-06-19 | 2012-07-27 | Alpharma Pharmaceuticals, Llc | Composiciones farmacéuticas |
PL2679228T3 (pl) | 2006-06-21 | 2018-07-31 | Opko Ireland Global Holdings, Ltd. | Terapia z użyciem środka do uzupełniania witaminy D i środka do zastępowania hormonami witaminy D |
MX2008015996A (es) * | 2006-06-23 | 2009-01-20 | Esteve Labor Dr | Combinacion de un inhibidor de la colinesterasa y un compuesto con afinidad por el receptor 5-ht6. |
SA07280459B1 (ar) | 2006-08-25 | 2011-07-20 | بيورديو فارما إل. بي. | أشكال جرعة صيدلانية للتناول عن طريق الفم مقاومة للعبث تشتمل على مسكن شبه أفيوني |
DE102007011485A1 (de) | 2007-03-07 | 2008-09-11 | Grünenthal GmbH | Darreichungsform mit erschwertem Missbrauch |
DK2481400T3 (da) | 2007-04-25 | 2014-09-29 | Opko Ip Holdings Ii Inc | Orale præparater med kontrolleret frigivelse omfattende en vitamin D-forbindelse og en voksagtig bærer |
CA2683628C (en) | 2007-04-25 | 2018-03-06 | Cytochroma Inc. | Method of treating vitamin d insufficiency and deficiency |
US20080318994A1 (en) | 2007-06-21 | 2008-12-25 | Endo Pharmaceuticals, Inc. | Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instruction on Dosing for Renal Impairment |
US8623418B2 (en) | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
EP2249811A1 (en) | 2008-01-25 | 2010-11-17 | Grünenthal GmbH | Pharmaceutical dosage form |
US20090246276A1 (en) * | 2008-01-28 | 2009-10-01 | Graham Jackson | Pharmaceutical Compositions |
CN102123701B (zh) | 2008-05-09 | 2013-03-27 | 格吕伦塔尔有限公司 | 使用喷雾冻凝步骤制备中间粉末制剂以及最终固体剂型的方法 |
US20100003322A1 (en) * | 2008-07-03 | 2010-01-07 | Lai Felix S | Enteric coated hydrophobic matrix formulation |
WO2010099508A1 (en) | 2009-02-26 | 2010-09-02 | Theraquest Biosciences, Inc. | Extended release oral pharmaceutical compositions of 3-hydroxy-n-methylmorphinan and method of use |
ES2706407T3 (es) | 2009-03-10 | 2019-03-28 | Euro Celtique Sa | Composiciones farmacéuticas de liberación inmediata que comprenden oxicodona y naloxona |
JP2012533585A (ja) | 2009-07-22 | 2012-12-27 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 酸化感受性オピオイドのための不正使用防止剤形 |
NZ596667A (en) | 2009-07-22 | 2013-09-27 | Gruenenthal Chemie | Hot-melt extruded controlled release dosage form |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
US10668060B2 (en) | 2009-12-10 | 2020-06-02 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
ES2606227T3 (es) | 2010-02-03 | 2017-03-23 | Grünenthal GmbH | Preparación de una composición farmacéutica en polvo mediante una extrusora |
CN102869349A (zh) * | 2010-03-09 | 2013-01-09 | 阿尔科米斯制药爱尔兰有限公司 | 耐酒精的肠溶药物组合物 |
LT2552484T (lt) | 2010-03-29 | 2020-04-27 | Opko Ireland Global Holdings, Ltd. | Būdai ir kompozicijos, skirti paratiroidų lygiams sumažinti |
BR112012028773A2 (pt) | 2010-05-10 | 2016-07-19 | Euro Celtique Sa | composições farmacêuticas compreendendo hidromorfona e naloxona |
EP2593141B1 (en) | 2010-07-16 | 2018-07-04 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
KR20130137627A (ko) | 2010-09-02 | 2013-12-17 | 그뤼넨탈 게엠베하 | 음이온성 중합체를 포함하는 내변조성 투여형 |
CA2808219C (en) | 2010-09-02 | 2019-05-14 | Gruenenthal Gmbh | Tamper resistant dosage form comprising inorganic salt |
CN103841964A (zh) | 2011-07-29 | 2014-06-04 | 格吕伦塔尔有限公司 | 提供药物立即释放的抗破碎片剂 |
NO2736497T3 (ja) | 2011-07-29 | 2018-01-20 | ||
CA2864949A1 (en) | 2012-02-28 | 2013-09-06 | Grunenthal Gmbh | Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer |
CA2868142A1 (en) | 2012-04-18 | 2013-10-24 | Grunenthal Gmbh | Tamper resistant and dose-dumping resistant pharmaceutical dosage form |
US10064945B2 (en) | 2012-05-11 | 2018-09-04 | Gruenenthal Gmbh | Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc |
US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
KR101847947B1 (ko) | 2013-03-15 | 2018-05-28 | 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 | 안정화되고 변형된 비타민 d 방출 제형 |
BR112015026549A2 (pt) | 2013-05-29 | 2017-07-25 | Gruenenthal Gmbh | forma de dosagem à prova de violação contendo uma ou mais partículas |
AU2014273226B2 (en) | 2013-05-29 | 2019-06-27 | Grunenthal Gmbh | Tamper resistant dosage form with bimodal release profile |
WO2015004245A1 (en) | 2013-07-12 | 2015-01-15 | Grünenthal GmbH | Tamper-resistant dosage form containing ethylene-vinyl acetate polymer |
NZ716267A (en) | 2013-07-23 | 2017-05-26 | Euro Celtique Sa | A combination of oxycodone and naloxone for use in treating pain in patients suffering from pain and a disease resulting in intestinal dysbiosis and/or increasing the risk for intestinal bacterial translocation |
WO2015037019A2 (en) * | 2013-09-15 | 2015-03-19 | Rubicon Research Private Limited | Modified release pharmaceutical formulations |
US9814710B2 (en) | 2013-11-13 | 2017-11-14 | Euro-Celtique S.A. | Hydromorphone and naloxone for treatment of pain and opioid bowel dysfunction syndrome |
BR112016010482B1 (pt) | 2013-11-26 | 2022-11-16 | Grünenthal GmbH | Preparação de uma composição farmacêutica em pó por meio de criomoagem |
WO2015173195A1 (en) | 2014-05-12 | 2015-11-19 | Grünenthal GmbH | Tamper resistant immediate release capsule formulation comprising tapentadol |
AU2015266117A1 (en) | 2014-05-26 | 2016-11-24 | Grunenthal Gmbh | Multiparticles safeguarded against ethanolic dose-dumping |
EP3193925A2 (en) | 2014-08-07 | 2017-07-26 | OPKO Ireland Global Holdings, Ltd. | Adjunctive therapy with 25-hydroxyvitamin d |
EP3285745A1 (en) | 2015-04-24 | 2018-02-28 | Grünenthal GmbH | Tamper-resistant dosage form with immediate release and resistance against solvent extraction |
FR3037789A1 (fr) * | 2015-06-23 | 2016-12-30 | Rondol Ind | Ligne de production pour la production de medicaments, et installation de production comprenant une telle ligne de production |
EP3346991A1 (en) | 2015-09-10 | 2018-07-18 | Grünenthal GmbH | Protecting oral overdose with abuse deterrent immediate release formulations |
CN108883120A (zh) | 2016-03-28 | 2018-11-23 | 欧普科爱尔兰环球控股有限公司 | 维生素d治疗方法 |
WO2017222575A1 (en) | 2016-06-23 | 2017-12-28 | Collegium Pharmaceutical, Inc. | Process of making more stable abuse-deterrent oral formulations |
WO2019087084A1 (en) | 2017-11-02 | 2019-05-09 | Eman Biodiscoveries Sd. Bhd. | Extract of orthosiphon stamineus, formulations, and uses thereof |
Family Cites Families (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3870790A (en) | 1970-01-22 | 1975-03-11 | Forest Laboratories | Solid pharmaceutical formulations containing hydroxypropyl methyl cellulose |
US3901969A (en) | 1973-09-10 | 1975-08-26 | Union Corp | Sustained release of methantheline |
US3901968A (en) | 1973-09-10 | 1975-08-26 | Union Corp | Sustained release of methantheline |
US4088798A (en) | 1975-11-11 | 1978-05-09 | Sandoz, Inc. | Methods for the preparation of controlled gastric residence time medicament formulations |
GB1561204A (en) | 1977-06-01 | 1980-02-13 | Ici Ltd | Sustained release pharmaceutical composition |
DE2904310A1 (de) | 1979-02-05 | 1980-08-07 | Boehringer Mannheim Gmbh | Formlinge mit retardierter wirkstofffreisetzung und verfahren zu deren herstellung |
US4548990A (en) | 1983-08-15 | 1985-10-22 | Ciba-Geigy Corporation | Crosslinked, porous polymers for controlled drug delivery |
IE56999B1 (en) | 1983-12-22 | 1992-03-11 | Elan Corp Plc | Pharmaceutical formulation |
JPS60166608A (ja) | 1984-02-08 | 1985-08-29 | Japan Atom Energy Res Inst | サンドイツチ構造をもつ徐放性複合体およびその製造方法 |
DE3586600T2 (de) | 1984-02-10 | 1993-02-18 | Benzon Pharma As | Dosierungsform eine vielzahl mit einer diffusionshuelle ueberzogener einheiten enthaltend. |
US4849229A (en) | 1984-03-26 | 1989-07-18 | Forest Laboratories, Inc. | Controlled release solid drug dosage forms based on mixtures of water soluble nonionic cellulose ethers and anionic surfactants |
US4795327A (en) | 1984-03-26 | 1989-01-03 | Forest Laboratories, Inc. | Controlled release solid drug dosage forms based on mixtures of water soluble nonionic cellulose ethers and anionic surfactants |
US4600645A (en) | 1985-01-31 | 1986-07-15 | Warner-Lambert Company | Process for treating dosage forms |
GB2170104A (en) | 1985-01-30 | 1986-07-30 | Warner Lambert Co | Coated pharmaceutical dosage forms |
US5186937A (en) | 1985-06-07 | 1993-02-16 | A.E.C. Societe De Chimie Organique Et Biologique | Composition for feeding ruminants |
GB8519310D0 (en) | 1985-07-31 | 1985-09-04 | Zyma Sa | Granular active substances |
GB8521494D0 (en) | 1985-08-29 | 1985-10-02 | Zyma Sa | Controlled release tablet |
IT1214629B (it) | 1985-08-29 | 1990-01-18 | Formenti Farmaceutici Spa | Procedimento di microincapsulazione di un medicamento,medicamento cosi'preparato,e composizioni farmaceutiche che lo comprendono |
US4837004A (en) | 1985-10-18 | 1989-06-06 | Eastman Kodak Company | Rumen-stable pellets |
IT1204294B (it) | 1986-03-11 | 1989-03-01 | Gentili Ist Spa | Metodo di fabbricazione di granulari atti a produzione di compresse rivestite,per uso orale,a rilascio controllato |
US4756911A (en) | 1986-04-16 | 1988-07-12 | E. R. Squibb & Sons, Inc. | Controlled release formulation |
US4810501A (en) | 1986-06-17 | 1989-03-07 | Warner-Lambert Company | Sustained release pharmaceutical preparations |
GB8707416D0 (en) | 1987-03-27 | 1987-04-29 | Wellcome Found | Pharmaceutical formulations |
JP2668880B2 (ja) | 1987-06-23 | 1997-10-27 | 日本油脂株式会社 | 被覆アミノ酸類の製造方法 |
US5068110A (en) | 1987-09-29 | 1991-11-26 | Warner-Lambert Company | Stabilization of enteric coated dosage form |
US5219621A (en) | 1987-10-16 | 1993-06-15 | Elan Corporation, Plc | Methods of treatment with diltiazem formulations |
FR2624732B1 (fr) | 1987-12-21 | 1991-02-15 | Synthelabo | Formulation pharmaceutique a liberation prolongee |
US4837033A (en) | 1987-12-22 | 1989-06-06 | Shin-Etsu Chemical Co., Ltd. | Method for the preparation of a coated solid medicament |
US5019397A (en) | 1988-04-21 | 1991-05-28 | Alza Corporation | Aqueous emulsion for pharmaceutical dosage form |
US5024842A (en) | 1988-04-28 | 1991-06-18 | Alza Corporation | Annealed coats |
US5009897A (en) | 1988-06-24 | 1991-04-23 | Abbott Laboratories | Pharmaceutical granules and tablets made therefrom |
US5085866A (en) | 1988-12-02 | 1992-02-04 | Southern Research Institute | Method of producing zero-order controlled-released devices |
CA2007055A1 (en) | 1989-01-06 | 1990-07-06 | Garth Boehm | Theophylline dosage form |
CA2007181C (en) | 1989-01-06 | 1998-11-24 | Angelo Mario Morella | Sustained release pharmaceutical composition |
US5202128A (en) | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
US5122384A (en) | 1989-05-05 | 1992-06-16 | Kv Pharmaceutical Company | Oral once-per-day organic nitrate formulation which does not induce tolerance |
US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
PH27186A (en) | 1989-09-07 | 1993-04-16 | Ciba Geigy Ag | Double-coated granules of disodium pamidronate |
JPH03232814A (ja) | 1990-02-08 | 1991-10-16 | Shin Etsu Chem Co Ltd | 徐放性錠剤の製造方法 |
US5077053A (en) | 1990-02-12 | 1991-12-31 | Warner-Lambert Company | Zein as a moisture barrier for sugarless edible compositions and method for preparing same |
US5158777A (en) | 1990-02-16 | 1992-10-27 | E. R. Squibb & Sons, Inc. | Captopril formulation providing increased duration of activity |
CA2036907C (en) | 1990-02-28 | 1996-10-22 | Yuzo Miura | 3-(substituted phenyl) pyrazole derivatives, a process for producing the same, herbicidal composition containing the same and method of controlling weeds using said composition |
US5178866A (en) | 1990-03-23 | 1993-01-12 | Alza Corporation | Dosage form for delivering drug to the intestine |
JP2558396B2 (ja) | 1990-06-28 | 1996-11-27 | 田辺製薬株式会社 | 放出制御型製剤 |
JPH04230625A (ja) | 1990-12-27 | 1992-08-19 | Standard Chem & Pharmaceut Corp Ltd | 噴霧乾燥したジクロフェナクナトリウムを含み腸溶性の被覆を有するマイクロカプセルからなる微分散した錠剤組成物の製造方法 |
US5286497A (en) | 1991-05-20 | 1994-02-15 | Carderm Capital L.P. | Diltiazem formulation |
ZA923474B (en) | 1991-05-20 | 1993-01-27 | Marion Merrell Dow Inc | Diltiazem formulation |
US5288505A (en) | 1991-06-26 | 1994-02-22 | Galephar P.R., Inc., Ltd. | Extended release form of diltiazem |
US5213811A (en) | 1991-09-13 | 1993-05-25 | Sterling Drug Inc. | Oral sustained-release drug compositions |
US5273760A (en) | 1991-12-24 | 1993-12-28 | Euroceltigue, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5472712A (en) | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
US5580578A (en) * | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
US5286493A (en) | 1992-01-27 | 1994-02-15 | Euroceltique, S.A. | Stabilized controlled release formulations having acrylic polymer coating |
US5968551A (en) * | 1991-12-24 | 1999-10-19 | Purdue Pharma L.P. | Orally administrable opioid formulations having extended duration of effect |
US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
US5160742A (en) | 1991-12-31 | 1992-11-03 | Abbott Laboratories | System for delivering an active substance for sustained release |
IL109460A (en) | 1993-05-10 | 1998-03-10 | Euro Celtique Sa | Controlled release formulation comprising tramadol |
DE4329794C2 (de) * | 1993-09-03 | 1997-09-18 | Gruenenthal Gmbh | Tramadolsalz enthaltende Arzneimittel mit verzögerter Wirkstofffreisetzung |
JP3232814B2 (ja) | 1993-09-22 | 2001-11-26 | ジェイエスアール株式会社 | 感熱記録媒体用インキ組成物 |
CA2186785A1 (en) | 1994-04-01 | 1995-10-12 | Yoichiro Nakai | Process for producing sustained-release tablets and enteric tablets |
US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
WO1999001111A1 (en) * | 1997-07-02 | 1999-01-14 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
-
1998
- 1998-07-02 WO PCT/US1998/014087 patent/WO1999001111A1/en active IP Right Grant
- 1998-07-02 CA CA002270975A patent/CA2270975C/en not_active Expired - Lifetime
- 1998-07-02 EP EP98933239A patent/EP1009387B1/en not_active Expired - Lifetime
- 1998-07-02 DK DK98933239T patent/DK1009387T3/da active
- 1998-07-02 AT AT98933239T patent/ATE322892T1/de active
- 1998-07-02 PT PT98933239T patent/PT1009387E/pt unknown
- 1998-07-02 ES ES98933239T patent/ES2263211T3/es not_active Expired - Lifetime
- 1998-07-02 AU AU82934/98A patent/AU8293498A/en not_active Abandoned
- 1998-07-02 US US09/109,615 patent/US6306438B1/en not_active Expired - Lifetime
- 1998-07-02 JP JP50747799A patent/JP3739410B2/ja not_active Expired - Lifetime
- 1998-07-02 DE DE69834195T patent/DE69834195T2/de not_active Expired - Lifetime
-
2001
- 2001-10-19 US US10/052,844 patent/US6645527B2/en not_active Expired - Lifetime
-
2003
- 2003-05-19 JP JP2003140053A patent/JP4576097B2/ja not_active Expired - Lifetime
-
2006
- 2006-07-03 CY CY20061100915T patent/CY1106112T1/el unknown
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JP2001288117A (ja) * | 2000-04-05 | 2001-10-16 | Otsuka Pharmaceut Co Ltd | 医薬製剤用組成物 |
JP4570725B2 (ja) * | 2000-04-05 | 2010-10-27 | 大塚製薬株式会社 | 医薬製剤用組成物 |
JP2004534056A (ja) * | 2001-06-08 | 2004-11-11 | エンドー ファーマシューティカルズ, インコーポレイティド | アクリルポリマーを使用する制御放出投薬形態、およびそれを作製するためのプロセス |
JP2006507277A (ja) * | 2002-10-25 | 2006-03-02 | ラボファーマ インコーポレイテッド | 24時間有効な持続放出トラマドール製剤 |
JP2006516969A (ja) * | 2003-01-23 | 2006-07-13 | アモレパシフィック コーポレーション | 徐放性製剤及びその製造方法 |
JP2008509193A (ja) * | 2004-08-13 | 2008-03-27 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | プラミペキソール又はその薬学的に許容しうる塩を含有する徐放性ペレット製剤、その製法及び使用 |
JP2008528534A (ja) * | 2005-01-28 | 2008-07-31 | ユーロ−セルティーク エス.エイ. | 耐アルコール性剤形 |
JP2013100306A (ja) * | 2005-01-28 | 2013-05-23 | Euro-Celtique Sa | 耐アルコール性剤形 |
JP2009513717A (ja) * | 2005-10-31 | 2009-04-02 | アルザ・コーポレーシヨン | オピオイド徐放性経口投与製剤に対するアルコール誘発の用量ダンピングの軽減方法 |
JP2013526510A (ja) * | 2010-05-10 | 2013-06-24 | ユーロ−セルティーク エス.エイ. | 活性剤を負荷した顆粒と追加の活性剤の組合せ |
JP2013526509A (ja) * | 2010-05-10 | 2013-06-24 | ユーロ−セルティーク エス.エイ. | 活性剤を含まない顆粒およびその顆粒を含む錠剤の製造 |
JP2022500367A (ja) * | 2018-09-07 | 2022-01-04 | アール.ピー.シェーラー テクノロジーズ,エルエルシー | 硬化および低hlb界面活性剤の添加による固体または半固体脂質ベースの剤形の安定化 |
Also Published As
Publication number | Publication date |
---|---|
US6645527B2 (en) | 2003-11-11 |
AU8293498A (en) | 1999-01-25 |
US20020102302A1 (en) | 2002-08-01 |
ATE322892T1 (de) | 2006-04-15 |
CY1106112T1 (el) | 2011-06-08 |
EP1009387A4 (en) | 2004-08-25 |
DK1009387T3 (da) | 2006-08-14 |
JP2004002419A (ja) | 2004-01-08 |
ES2263211T3 (es) | 2006-12-01 |
DE69834195T2 (de) | 2007-03-29 |
EP1009387B1 (en) | 2006-04-12 |
CA2270975A1 (en) | 1999-01-14 |
WO1999001111A1 (en) | 1999-01-14 |
US6306438B1 (en) | 2001-10-23 |
PT1009387E (pt) | 2006-08-31 |
DE69834195D1 (de) | 2006-05-24 |
JP4576097B2 (ja) | 2010-11-04 |
CA2270975C (en) | 2003-04-01 |
EP1009387A1 (en) | 2000-06-21 |
JP3739410B2 (ja) | 2006-01-25 |
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