CN1052398C - 球状药用制剂 - Google Patents

球状药用制剂 Download PDF

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CN1052398C
CN1052398C CN92105698A CN92105698A CN1052398C CN 1052398 C CN1052398 C CN 1052398C CN 92105698 A CN92105698 A CN 92105698A CN 92105698 A CN92105698 A CN 92105698A CN 1052398 C CN1052398 C CN 1052398C
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I·R·巴克斯顿
H·克里奇利
S·T·莱斯利
S·T·A·马尔考斯卡
D·A·普拉特
R·B·米勒
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Abstract

一种受控释放组合物，包括由硫氮酮或其药学上可接受的盐和可选的成球剂组成的球状核，所述核被一种受控释放材料涂覆。如果加入成球剂的话，最好选用微晶纤维素。乙基纤维素是优选的受控释放涂层。受控释放涂层最好包含增塑剂、表面活性剂和胶粘改性剂。

Description

球状药用制剂
本发明涉及一种受控释放制剂及其制备方法，尤其涉及含硫氮酮的控制释放制剂。
硫氮酮是一种钙拮抗剂，可用来治疗心脏病，例如心胶病和高血压。
本发明的目的是提供一种受控释放硫氮酮制剂，适于每日一次给药，治疗高血压和心绞痛。
因此，本发明提供包含球状核的受控释放制剂，该核由硫氮酮或其药学上可接受的盐组成，还可含有成球剂，并覆有受控释放层。
本发明所用的适当的药学上可接受的盐包括药学上可接受的酸加成盐。特别优选盐酸盐。
本发明的受控释放药用组合物能够在较长时间内缓慢释放药物，并且在该时间内延长药物作用时间以达到常规药物传送的效果。
“球状”一词是药学领域的常用词，它是指直径为0.1mm～2.5mm；尤其是0.5mm～2mm的球状粒子。
本发明球状核最好含40％～98％，含60％～85％更好，尤其含70％～85％(重量)硫氮酮或其药学上可接受的盐。
成球剂可以是任何适当的药学上可接受的材料。它可以与活性成分一起成球以形成球状核。优选的成球剂是微晶纤维素，所用的微晶纤维素可以是，例如阿维塞尔PH107或阿维塞尔PH102(商品名，FMC公司)。一般来说，当存在成球剂时，它占球状核的1％～60％(重量)，最好药15％～40％(重量)。
球状核还可含有其它药学上可接受赋形剂和稀释剂。使之易于成球，例如用糖(如蔗糖、右旋糖、麦芽糖或乳糖)或糖醇(例如甘露醇、木糖醇或山梨糖醇)。在球状核中还可含有着色剂。
球状核最好是涂覆允许硫氮酮在水性介质中控制速率释放的膜，适宜的涂膜材料可包括水不溶蜡和聚合物，例如聚甲基丙烯酸酯(例如商标为Eudragit的聚合物)或优选水不溶纤维素，特别是乙基纤维素。这膜涂层还可含水溶性聚合物，例如聚乙烯吡咯烷酮或最好是水溶性纤维素，例如羟丙基甲基纤维素和羟丙基纤维素。应当理解，水不溶材料与水溶性材料的比率取决于所要求的释放速度和所选村料的溶解度，水溶性聚合物与水不溶聚合物的比率以1∶20至1∶2为佳。受控释放涂层优选包括一种或多种本领域的常规增塑剂，例如酞酸二乙酯，但最好是癸二酸二丁酯；表面活性剂，例如山梨聚糖三油酸酯、山梨聚糖单月桂酸酯或优选多乙氧基醚80(商标为Tween80)和胶粘改性剂，例如滑石粉或优选胶质无水硅石。
当存在增塑剂时，其含量将取决于所选的特定增塑剂，一般，增塑剂的量为受控释放膜涂层的1％至25％(重量)。当存在表面活性剂时，其适宜存在量为受控膜涂层的1％至25％(重量)当存在胶粘改性剂时，其存在量也以受控释放膜涂层的1％至25％(重量)为宜。
优选的受控释放膜涂层包括50％至95％乙基纤维素，5％至15％胶质无水硅石，5％至15％癸二酸二丁酯和5％至15％多乙氧基醚80(商标为Tween80)。
采用传统涂覆方法例如流化床或槽式涂覆，可在含硫氮酮的球状核的表面形成受控释放涂膜层。该涂层材料可应用溶液或悬浮液，适宜的溶剂系统包括水、二氯甲烷、乙醇、甲醇、异丙醇和丙酮及其混合物。涂覆溶液或悬浮液优选含2％至60％(重量)、最好含2％至20％(重量)涂覆材料。
受控释放涂覆材料的用量取决于所要求的释放速率，但是一般为受控释放涂覆球体的1％至25％(重量)，最好为2％至8％(重量)。
本发明含硫氮酮球体的制备方法包括以下步骤：
(a)将包括硫氮酮或其药学上可接受的盐、水和可选的成球剂的混合物成粒；
(b)挤压成粒混合物，得到挤出物；
(c)将挤出物成球，直至形成球状核；
(d)干燥球状核；并且
(e)膜涂覆球状核。
采用传统制药技术可将本发明组合物填充制成胶囊或压制成片剂。
本发明组合物的可适当地每日一次给药。一般每日一次给药，剂型中硫氮)酮或其药学上可接受的盐(优选硫氮酮盐酸盐)的含量为120mg～300mg。
为了更好地理解本发明，给出下述实施例，仅为说明而已。实施例1
制备了具有下述配方的胶囊
硫氮酮球状核
材料                                           毫克
硫氮酮盐酸盐U.S.P                            120
微晶纤维素E.P(Avicel PH 101)                   30.0
蒸馏水E.P                                      适量
                                               150
受控释放膜涂层
材料                                           毫克
硫氮酮盐酸盐球状核                           150
乙基纤维素N10 U.S.N.F                          7.38胶质无水硅石E.P.(Aerosil 130)                   0.988癸二酸二丁酯U.S.N.F.                            0.742多乙氧基醚80 E.P.(Tween 80)                     0.791二氯甲烷BS 1994                                 适量甲醇B.P.1973                                    适量
                                            160胶囊制剂                                        mg硫氮酮受控释放球状体                          160硬酯酸镁 EP                                     0.480明胶囊壳3号(Size 3)
采用高剪切混合器混合硫氮酮和微晶纤维素，该混合是湿式成粒，挤压后得到挤出物，成粒并置于流化床干燥器中干燥，所得球体过筛，得到粒径为0.85-1.7毫米。
将受控释放涂膜成分分散在二氯甲烷/甲醇溶剂体系中，应用到流化床涂敷器内的硫氮酮球状核上，得到的涂膜球体过筛，然后，在流化床涂覆器中，将含硫氮酮受控释放球体用双氢氯噻嗪和羟丙基甲基纤维素的分散体涂膜。
通过EP篮式装置(100转/分)，用PH4.5EP磷酸盐缓冲液测定所得产品的溶解度。所得结果如下：
硫氮酮溶解度
时间(小时)                               硫氮酮受控释放
                                           球状体
2                                    23
3                                    37
4                                    48
5                                    57
6                                    63
8                                    72
10                                   77
12                                   81
15                                   86
20                                   90

Claims (14)

1.一种受控释放组合物的制备方法，所制备的组合物含有由硫氮酮或其药学上可接受的盐、水和微晶纤维素以及任意选择的一种糖和/或一种糖醇和/或一种着色剂；该方法包括：
(a)使由60％至98％重量的硫氮酮或其药学上可接受的盐、水和微晶纤维素以及任意选择的一种糖和/或一种着色剂组成的混合物形成颗粒；
(b)将该颗粒化的混合物挤压出，以得到一种挤出物；
(c)将该挤出物球状化直至球状核形成；
(d)使该球状核干燥；以及
(e)用受控释放的物质涂覆该球状核。
2.根据权利要求1的方法，其中该颗粒状混合物含有70％至85％重量的硫氮酮或其药学上可接受的盐。
3.根据权利要求1的方法，其中该微晶纤维素的含量为球状核重量的15％至40％。
4.根据权利要求1的方法，其中该受控释放涂覆材料包括一种水不溶的聚合物。
5.根据权利要求4的方法，其中涂覆材料包括乙基纤维素。
6.根据权利要求1至5的任一项权利要求的方法，其中受控释放物质进一步包括一种或多种增塑剂、表面活性剂和粘胶改性剂。
7.按照权利要求6的方法，其中受控释放涂层包括50％～95％乙基纤维素、5％～15％胶状无水硅石、5％～15％癸二酸二丁酯和5％～15％多乙氧基醚80。
8.按照权利要求1至5任一项权利要求的方法，其中，受控释放涂覆材料的用量为受控释放的组合物重量的2％～8％。
9.按照权利要求6的方法，其中受控释放涂覆材料的用量为受控释放的组合物重量的2％～8％。
10.按照权利要求7的方法，其中受控释放涂覆材料的用量为受控释放的组合物重量的2％～8％。
11.根据权利要求1至5的任一项权利要求的方法，其中包括进一步将在步骤(e)中已涂覆的球状核填充入胶囊中的步骤。
12.根据权利要求6的方法，其中包括进一步将在步骤(e)中已涂覆的球状核填充入胶囊中的步骤。
13.根据权利要求7的方法，其中包括进一步在步骤(e)中已涂覆的球状核填充入胶囊中的步骤、
14.根据权利要求8的方法，其中包括进一步将在步骤(e)中已涂覆的球状核填充入胶囊中的步骤。
CN92105698A 1991-08-12 1992-08-12 球状药用制剂 Expired - Lifetime CN1052398C (zh)

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GB919122967A GB9122967D0 (en) 1991-10-29 1991-10-29 Pharmaceutical composition
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Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5266331A (en) * 1991-11-27 1993-11-30 Euroceltique, S.A. Controlled release oxycodone compositions
US5681585A (en) * 1991-12-24 1997-10-28 Euro-Celtique, S.A. Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US20080075781A1 (en) * 1992-11-25 2008-03-27 Purdue Pharma Lp Controlled release oxycodone compositions
FR2702160B1 (fr) * 1993-03-02 1995-06-02 Biovecteurs As Vecteurs particulaires synthétiques et procédé de préparation.
SE9301220D0 (sv) * 1993-04-14 1993-04-14 Kabi Pharmacia Ab Manufacturing matrices
US20070275062A1 (en) * 1993-06-18 2007-11-29 Benjamin Oshlack Controlled release oxycodone compositions
IL110014A (en) * 1993-07-01 1999-11-30 Euro Celtique Sa Solid controlled-release oral dosage forms of opioid analgesics
US7740881B1 (en) 1993-07-01 2010-06-22 Purdue Pharma Lp Method of treating humans with opioid formulations having extended controlled release
US5834024A (en) * 1995-01-05 1998-11-10 Fh Faulding & Co. Limited Controlled absorption diltiazem pharmaceutical formulation
GB9519363D0 (en) 1995-09-22 1995-11-22 Euro Celtique Sa Pharmaceutical formulation
US5914134A (en) * 1997-01-27 1999-06-22 Wockhardt Europe Limited Process for the pulsatile delivery of diltiazem HCL and product produced thereby
US7060734B1 (en) 1997-09-09 2006-06-13 Alza Corporation Pharmaceutical coating composition and method of use
AU9221898A (en) * 1997-09-09 1999-03-29 Alza Corporation Pharmaceutical coating composition and method of use
US5891845A (en) * 1997-11-21 1999-04-06 Fuisz Technologies Ltd. Drug delivery systems utilizing liquid crystal structures
HUP0100310A3 (en) * 1997-12-22 2002-11-28 Euro Celtique Sa A method of preventing abuse of opioid dosage forms
CA2314893C (en) 1997-12-22 2005-09-13 Euro-Celtique, S.A. Opioid agonist/antagonist combinations
US6524620B2 (en) 1998-07-20 2003-02-25 Andrx Pharmaceuticals, Inc. Diltiazem controlled release formulation and method of manufacture
US6806294B2 (en) 1998-10-15 2004-10-19 Euro-Celtique S.A. Opioid analgesic
US6432448B1 (en) 1999-02-08 2002-08-13 Fmc Corporation Edible coating composition
US6723342B1 (en) 1999-02-08 2004-04-20 Fmc Corporation Edible coating composition
US6410255B1 (en) * 1999-05-05 2002-06-25 Aurora Biosciences Corporation Optical probes and assays
BR0011522A (pt) 1999-05-14 2002-06-04 Nereus Pharmaceuticals Inc Composto e método de sintetização para a fabricação do composto
GB9913979D0 (en) 1999-06-17 1999-08-18 Univ Wales Medicine Spheroid preparation
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
MXPA02004293A (es) 1999-10-29 2002-10-31 Euro Celtique Sa Formulaciones de hidrocodona de liberacion controlada..
US6500462B1 (en) 1999-10-29 2002-12-31 Fmc Corporation Edible MCC/PGA coating composition
US7108866B1 (en) 1999-12-10 2006-09-19 Biovall Laboratories International Srl Chronotherapeutic diltiazem formulations and the administration thereof
US20060153914A1 (en) * 1999-12-10 2006-07-13 Biovail Laboratories International S.R.L. Chronotherapeutic diltiazem formulations and the administration thereof
EP1299104B1 (en) 2000-02-08 2009-05-13 Euro-Celtique S.A. Tamper-resistant oral opioid agonist formulations
JP2003523769A (ja) * 2000-02-23 2003-08-12 ヴァーテックス ファーマシューティカルズ （サンディエゴ）エルエルシー 改変された蛍光タンパク質
US6852031B1 (en) * 2000-11-22 2005-02-08 Igt EZ pay smart card and tickets system
US6635277B2 (en) 2000-04-12 2003-10-21 Wockhardt Limited Composition for pulsatile delivery of diltiazem and process of manufacture
GB0025208D0 (en) * 2000-10-13 2000-11-29 Euro Celtique Sa Delayed release pharmaceutical formulations
EP1337244A4 (en) * 2000-10-30 2006-01-11 Euro Celtique Sa HYDROCODON FORMULATIONS WITH CONTROLLED RELEASE
ES2402045T3 (es) * 2000-11-16 2013-04-26 The Regents Of The University Of California Taxón de actionomiceto marino para el descubrimiento de fármacos y de productos de fermentación
TR200300731T2 (tr) 2000-11-28 2004-08-23 Fmc Corporation Yenebilir PGA kaplama bileşimi
UA81224C2 (uk) * 2001-05-02 2007-12-25 Euro Celtic S A Дозована форма оксикодону та її застосування
US20110104214A1 (en) 2004-04-15 2011-05-05 Purdue Pharma L.P. Once-a-day oxycodone formulations
DE60238756D1 (de) 2001-05-11 2011-02-10 Endo Pharmaceuticals Inc Opioid enthaltende arzneiform gegen missbrauch
CA2454328C (en) 2001-07-18 2008-03-18 Christopher D. Breder Pharmaceutical combinations of oxycodone and naloxone
CA2457361C (en) 2001-08-06 2008-11-04 Christopher Breder Opioid agonist formulations with releasable and sequestered antagonist
WO2003013433A2 (en) 2001-08-06 2003-02-20 Euro-Celtique S.A. Sequestered antagonist formulations
US20030044458A1 (en) 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US20030181488A1 (en) * 2002-03-07 2003-09-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof
EP2425821B1 (en) 2002-04-05 2017-05-10 Euro-Celtique S.A. Pharmaceutical preparation containing oxycodone and naloxone
US7176232B2 (en) 2002-06-24 2007-02-13 The Regents Of The University Of California Salinosporamides and methods for use thereof
EP2422773A3 (en) 2002-09-20 2012-04-18 Alpharma, Inc. Sequestering subunit and related compositions and methods
US7112581B2 (en) * 2002-09-27 2006-09-26 Nereus Pharmaceuticals, Inc. Macrocyclic lactams
US20040202717A1 (en) * 2003-04-08 2004-10-14 Mehta Atul M. Abuse-resistant oral dosage forms and method of use thereof
US20040208932A1 (en) * 2003-04-17 2004-10-21 Ramachandran Thembalath Stabilized paroxetine hydrochloride formulation
MY135852A (en) 2003-04-21 2008-07-31 Euro Celtique Sa Pharmaceutical products
WO2005002572A2 (en) * 2003-06-20 2005-01-13 Nereus Pharmaceuticals, Inc. Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases
EP2441767B1 (en) * 2003-06-20 2015-06-10 The Regents of The University of California Salinosporamides and methods for use thereof
US7727752B2 (en) * 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
CA2445420A1 (en) * 2003-07-29 2005-01-29 Invitrogen Corporation Kinase and phosphatase assays
US7619059B2 (en) * 2003-07-29 2009-11-17 Life Technologies Corporation Bimolecular optical probes
ATE458200T1 (de) * 2003-09-12 2010-03-15 Life Technologies Corp Anwendungen des resonanzenergietransfers zwischen terbium und gfp
KR20060132698A (ko) * 2004-01-23 2006-12-21 니리어스 파마슈티컬즈, 인코퍼레이션 항균제로 유용한 비스-인돌 피롤
US7579371B2 (en) 2004-04-30 2009-08-25 Nereus Pharmaceuticals, Inc. Methods of using [3.2.0] heterocyclic compounds and analogs thereof
JP2007535559A (ja) 2004-04-30 2007-12-06 ネレアス ファーマシューティカルズ インコーポレイテッド ［３．２．０］複素環式化合物及びその使用法
EP1604666A1 (en) 2004-06-08 2005-12-14 Euro-Celtique S.A. Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD)
US7619007B2 (en) 2004-11-23 2009-11-17 Adamas Pharmaceuticals, Inc. Method and composition for administering an NMDA receptor antagonist to a subject
DE05852057T1 (de) 2004-11-23 2007-11-29 Neuromolecular Pharmaceuticals Inc., Emeryville Zusammensetzung aus einer beschichtung oder matrix mit verzögerter freisetzung und einem nmda-rezeptorantagonisten sowie verfahren zur verabreichung eines solchen nmda-rezeptorantagonisten an ein subjekt
WO2006058236A2 (en) 2004-11-24 2006-06-01 Neuromolecular Pharmaceuticals, Inc. Composition comprising an nmda receptor antagonist and levodopa and use thereof for treating neurological disease
CN101155582B (zh) 2004-12-03 2013-04-24 达纳-法伯癌症研究公司 治疗肿瘤性疾病的组合物和方法
EP1702558A1 (en) 2005-02-28 2006-09-20 Euro-Celtique S.A. Method and device for the assessment of bowel function
AU2006228536A1 (en) * 2005-03-31 2006-10-05 Rafael Armament Development Authority Ltd. Spherically shaped substances
DE602006016934D1 (de) 2005-04-06 2010-10-28 Adamas Pharmaceuticals Inc Verfahren und zusammensetzungen zur behandlung von zns-erkrankungen
ATE556046T1 (de) 2005-07-21 2012-05-15 Nereus Pharmaceuticals Inc Interleukin-1- und tumornekrosefaktor-a- modulatoren, synthese solcher modulatoren und verfahren unter anwendung solcher modulatoren
KR20140079441A (ko) 2006-06-19 2014-06-26 알파마 파머슈티컬스 엘엘씨 약제학적 조성물
AU2007275034A1 (en) * 2006-07-21 2008-01-24 Lab International Srl Hydrophilic abuse deterrent delivery system
EP1920767A1 (en) * 2006-11-09 2008-05-14 Abbott GmbH & Co. KG Melt-processed imatinib dosage form
WO2008095195A2 (en) * 2007-02-02 2008-08-07 Nereus Pharmaceuticals, Inc. Lyophilized formulations of salinosporamide a
US20090017167A1 (en) * 2007-07-11 2009-01-15 Herbalife International Inc. Mixture and beverage made therefrom for protecting cellular hydration
US8394816B2 (en) * 2007-12-07 2013-03-12 Irene Ghobrial Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia
US20100266645A1 (en) * 2007-12-17 2010-10-21 Alfred Liang Pharmaceutical compositions
US20100151014A1 (en) * 2008-12-16 2010-06-17 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
RU2010129907A (ru) * 2007-12-17 2012-01-27 Лабофарм Инк. (CA) Лекарственная форма с контролируемым высвобождением, предотвращающая неправильное употребление
US8623418B2 (en) 2007-12-17 2014-01-07 Alpharma Pharmaceuticals Llc Pharmaceutical composition
CN102089312A (zh) 2008-05-12 2011-06-08 尼瑞斯药品公司 作为蛋白酶体抑制剂的Salinosporamide衍生物
WO2010003963A1 (en) * 2008-07-07 2010-01-14 Euro-Celtique S.A. Use of opioid antagonists for treating urinary retention
JP5886632B2 (ja) 2009-03-10 2016-03-16 ユーロ−セルティーク エス．エイ． オキシコドンおよびナロキソンを含む即時放出医薬組成物
AU2010325960C1 (en) 2009-12-02 2015-08-06 Adamas Pharma, Llc Amantadine compositions and methods of use
US10463611B2 (en) 2011-06-08 2019-11-05 Sti Pharma, Llc Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
ITFI20110172A1 (it) * 2011-08-08 2013-02-09 Valpharma Sa Formulazione multiparticolata a rilascio modificato di diltiazem hcl.
US10154971B2 (en) 2013-06-17 2018-12-18 Adamas Pharma, Llc Methods of administering amantadine
KR20160034352A (ko) 2013-07-23 2016-03-29 유로-셀티큐 에스.에이. 장내 세균총이상을 초래하고/하거나 장내 박테리아 전위에 대한 위험을 증가시키는 질환과 통증으로 인해 고통받고 있는 환자에서 통증을 치료하는데 사용하기 위한 옥시코돈과 날록손의 조합물
MX2017002750A (es) 2014-09-02 2017-08-02 Singh Bhupinder Metodo para marcar una molecula deuterada o no deuterada y formulaciones farmaceuticas para tratamiento.
WO2016057563A1 (en) 2014-10-08 2016-04-14 Pacific Northwest Diabetes Research Institute Methods and compositions for increasing the potency of antifungal agents
US10973783B2 (en) 2015-12-30 2021-04-13 Adamas Pharmaceuticals, Inc. Methods and compositions for the treatment of seizure-related disorders
WO2018200885A1 (en) 2017-04-26 2018-11-01 Neurocentria, Inc. Magnesium compositions and methods of use
JP2021519367A (ja) 2018-03-28 2021-08-10 ハーバライフ・インターナショナル・オブ・アメリカ・インコーポレイテッド 多糖のアセチル化

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0304105A1 (en) * 1987-07-30 1989-02-22 SCHELDE-DELTA, b.v.b.a. Process and apparatus for fixing materials in a fluid stream
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
EP0322277A1 (fr) * 1987-12-21 1989-06-28 Synthelabo Formulation pharmaceutique à libération prolongée
EP0340105A1 (fr) * 1988-04-27 1989-11-02 Sanofi Microbilles de diltiazem, leur procédé de fabrication et compositions pharmaceutiques à libération prolongée les contenant

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4456628A (en) * 1981-01-07 1984-06-26 Bauer Kurt H Process for film-coating a particulate solid, and emulsions for conducting the process
DK152744C (da) * 1982-08-13 1988-10-31 Benzon As Alfred Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat
US4898729A (en) * 1983-12-09 1990-02-06 Euroceltique, S.A. Treatment of hypertension, compounds and compositions for antihypertension and diuresis
US4894240A (en) * 1983-12-22 1990-01-16 Elan Corporation Plc Controlled absorption diltiazem formulation for once-daily administration
IE56999B1 (en) * 1983-12-22 1992-03-11 Elan Corp Plc Pharmaceutical formulation
US4917899A (en) * 1983-12-22 1990-04-17 Elan Corporation Plc Controlled absorption diltiazem formulation
US5002776A (en) * 1983-12-22 1991-03-26 Elan Corporation, Plc Controlled absorption diltiazem formulations
US5364620A (en) * 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration
DE3403329A1 (de) * 1984-02-01 1985-08-01 Horst Dr. 4019 Monheim Zerbe Pharmazeutisches produkt in form von pellets mit kontinuierlicher, verzoegerter wirkstoffabgabe
US4643731A (en) * 1985-08-16 1987-02-17 Alza Corporation Means for providing instant agent from agent dispensing system
JPS62103012A (ja) * 1985-10-23 1987-05-13 Eisai Co Ltd 多重顆粒
IT1200217B (it) * 1986-09-30 1989-01-05 Valducci Roberto Membrana per uso farmaceutico ed industriale
DE3709188A1 (de) * 1987-03-20 1988-09-29 Mannesmann Ag Ausgiessrohr fuer metallurgische gefaesse
GB8707421D0 (en) * 1987-03-27 1987-04-29 Wellcome Found Pharmaceutical formulations
CA1323833C (en) * 1987-04-28 1993-11-02 Yatindra M. Joshi Pharmaceutical compositions in the form of beadlets and method
US4814181A (en) * 1987-09-03 1989-03-21 Alza Corporation Dosage form comprising fast agent delivery followed by slow agent delivery
US5219621A (en) * 1987-10-16 1993-06-15 Elan Corporation, Plc Methods of treatment with diltiazem formulations
DE3856555T2 (de) * 1987-10-16 2004-04-29 Elan Corp. Plc Diltiazem-Zusammensetzungen mit kontrollierter Wirkstoffabsorption
IL88083A (en) * 1987-11-06 1992-11-15 Tanabe Seiyaku Co Controlled release pharmaceutical dosage form and its preparation
DE3739779A1 (de) * 1987-11-24 1989-06-08 Beiersdorf Ag Pharmazeutische praeparate
FR2623714B1 (fr) * 1987-11-26 1990-04-20 Ethypharm Sa Forme a liberation prolongee du diltiazem, et son medicament ainsi obtenu
JP2643222B2 (ja) * 1988-02-03 1997-08-20 エーザイ株式会社 多重層顆粒
GB8805695D0 (en) * 1988-03-10 1988-04-07 Nycomed As Enteric coated spheroidal granules
FI101344B (fi) * 1988-03-31 1998-06-15 Tanabe Seiyaku Co Menetelmä valmistaa valmiste, josta kontrolloidusti vapautuu farmaseut tisesti aktiivista ainetta
EP0373417A1 (en) * 1988-11-30 1990-06-20 Schering Corporation Sustained release diltiazem formulation
SE506179C2 (sv) * 1989-01-23 1997-11-17 Ciba Geigy Ag Farmaceutisk lågkomposition av benazepril och ett tiaziddiuretikum
SE8902699D0 (sv) * 1989-08-09 1989-08-09 Lejus Medical Ab Diltiazem containing pharmaceutical compositios
JPH0674206B2 (ja) * 1989-12-28 1994-09-21 田辺製薬株式会社 放出制御型製剤およびその製法
IT1241417B (it) * 1990-03-06 1994-01-14 Vectorpharma Int Composizioni terapeutiche a rilascio controllato di farmaci supportatisu polimeri reticolati e rivestiti con film polimerici,e loro processodi preparazione
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

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
US4808413B1 (zh) * 1987-04-28 1991-09-10 Squibb & Sons Inc
EP0304105A1 (en) * 1987-07-30 1989-02-22 SCHELDE-DELTA, b.v.b.a. Process and apparatus for fixing materials in a fluid stream
EP0322277A1 (fr) * 1987-12-21 1989-06-28 Synthelabo Formulation pharmaceutique à libération prolongée
EP0340105A1 (fr) * 1988-04-27 1989-11-02 Sanofi Microbilles de diltiazem, leur procédé de fabrication et compositions pharmaceutiques à libération prolongée les contenant

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JPH05201867A (ja) 1993-08-10
ATE165513T1 (de) 1998-05-15
ES2115643T3 (es) 1998-07-01
IL102778A0 (en) 1993-01-31
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AU651715B2 (en) 1994-07-28
DE69225278D1 (de) 1998-06-04
PH31288A (en) 1998-07-06
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FI923582A (fi) 1993-02-13
NO923128L (no) 1993-02-15
US5601845A (en) 1997-02-11
NO923128D0 (no) 1992-08-11
EP0527637B1 (en) 1998-04-29
IL102778A (en) 1999-05-09
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NO304406B1 (no) 1998-12-14
US5670172A (en) 1997-09-23
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CA2075356A1 (en) 1993-02-13
CN1069408A (zh) 1993-03-03

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