CN1099262A - 控制释放制剂 - Google Patents
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Abstract
本发明涉及一种用于口服给药的控制释放制剂,
它含有反胺苯环醇或其可药用盐作为活性成分。
Description
本发明涉及用于口服给药的控制释放制剂、其制备方法及其医疗应用。具体地讲,本发明涉及包含反胺苯环醇(tramadol)或其可药用盐的控制释放制剂。
反胺苯环醇,其化学名为(±)-反式-2-[(二甲基氨基)甲基]-1-(3-甲氧基苯基)环己醇,是一种口服活性鸦片类(opioid)止痛药。含有反胺苯环醇或者更具体地讲含有其盐酸盐的常规释放的胶囊剂、滴剂和栓剂已经市售了许多年,用于治疗中度疼痛至剧痛;但是这类制剂不能控制释放反胺苯环醇。此外,尽管长期使用反胺苯环醇,但是含有反胺苯环醇作为活性成分的用于口服给药的控制释放制剂以前甚至从未在文献中描述过。
本发明的一个目的是提供了适于至少每12小时(例如最高达24小时)给药一次的用于治疗疼痛的口服控制释放反胺苯环醇制剂。
因此本发明提供了包含反胺苯环醇或其可药用盐的用于口服给药的控制释放制剂。
适用于本发明的反胺苯环醇的可药用盐是本领域中通常已知的那些可药用盐,例如可药用酸加成盐。特别优选盐酸盐。
本发明的控制释放制剂是在延长的时间期间内可达到药物的缓慢释放的制剂,因此对比常规释放的药物而言延长了药物作用的持续时间。优选的此类制剂在12小时或更长的治疗时间内保持血药浓度。
本发明人发现,为了在口服给药后至少12小时期间能够控制释放反胺苯环醇,体外释放速率优选相应于下列反胺苯环醇的释放速率%:
表1 | |
时间(小时) | 释放% |
1 | 0-50 |
2 | 0-75 |
4 | 3-95 |
8 | 10-100 |
12 | 20-100 |
16 | 30-100 |
24 | 50-100 |
36 | >80 |
尤其适用于每天两次给药的另一类优选的制剂具有相应于下列反胺苯环醇释放速率%的体外释放速率:
表2 | |
时间(小时) | 释放% |
1 | 20-50 |
2 | 40-75 |
4 | 60-95 |
8 | 80-100 |
12 | 90-100 |
特别适用于每天一次给药的另一类优选的制剂具有相应于下列反胺苯环醇释放速率%的体外释放速率:
表3 | |
时间(小时) | 释放% |
1 | 0-50 |
2 | 0-75 |
4 | 10-95 |
8 | 35-100 |
12 | 55-100 |
16 | 70-100 |
24 | >90 |
此外,本发明还有一类优选的、也特别适用于每天一次给药的制剂具有相应于下列反胺苯环醇释放速率%的体外释放速率:
表4 | |
时间(小时) | 释放% |
1 | 0-30 |
2 | 0-40 |
4 | 3-55 |
8 | 10-65 |
12 | 20-75 |
16 | 30-88 |
24 | 50-100 |
36 | >80 |
每天一次给药的更优选的制剂具有基本如下的体外释放速率:
表5 | |
时间(小时) | 反胺苯环醇释放% |
1 | 10-30 |
2 | 17-37 |
4 | 27-47 |
8 | 40-60 |
12 | 49-69 |
16 | 57-77 |
本发明每天两次给药的控制释放制剂一旦释放,另一种优选的体外溶解速率是:1小时后反胺苯环醇释放5-50%(重量)、2小时后反胺苯环醇释放10-75%(重量)、4小时后反胺苯环醇释放20-95%(重量)、8小时后反胺苯环醇释放40-100%(重量)、12小时后反胺苯环醇释放超过50%(重量)、18小时后反胺苯环醇释放超过70%(重量)、24小时后反胺苯环醇释放超过80%(重量)。
另外,在每天两次给药的控制释放制剂的情况下,优选的是:口服给药8小时后在体内吸收70-95%(重量)反胺苯环醇、10小时后吸收77-97%(重量)反胺苯环醇、12小时后吸收80-100%(重量)反胺苯环醇。
适于每天两次给药的本发明制剂的tmax可为1.5-8小时,优选2-7小时,W50值为7-16小时。
适于每天一次给药的本发明制剂的tmax可为3-16小时,优选4-5小时,W50值为10-33小时。
参数W50定义了在50%Cmax的血浆分布图的宽度,即血浆浓度等于或大于50%峰浓度的持续时间。该参数是通过所测数据的线性内推法测定的,它表示在血浆分布图中在第一个(或唯一的)上斜面交叉与最后一个(或唯一的)下斜面交叉之间的时间差。
除非另外指明,本文所提及的体外释放速率是采用Ph.Eur.Paddle方法在100rpm在900ml0.1N盐酸中在37℃以及在270nm处采用UV检测得到的。
本发明的控制释放制剂优选含有止痛有效量的反胺苯环醇或其可药用盐,通常每个剂量单位含有50-800mg,特别是100、200、300、400至600mg(以反胺苯环醇盐酸盐计)。
本发明的控制释放制剂可以是例如粒剂、球剂(spheroids)、小丸剂、多颗粒剂、胶囊剂、片剂、香囊剂(sachets)、控制释放悬浮液剂,或为结合这类粒剂、球剂、小丸剂或多颗粒剂的任何其他适宜的剂型。
本发明制剂中的活性成分适于与基质结合。基质可以是任何能在至少12小时期间内控制释放反胺苯环醇的基质,优选能提供在上述范围内的反胺苯环醇的体外溶解速率和体内吸收速率的基质。优选该基质为控制释放基质。或者可以使用带有包衣的正常释放基质,该包衣可以控制释放活性成分。
包括在控制释放基质中的适宜物质包括:
(a)亲水性或疏水性聚合物,如树胶、纤维素醚、丙烯酸树脂和蛋白质衍生物质。在这些聚合物中,优选纤维素醚,特别是烷基纤维素。该制剂通常可含有1%-80%(重量)的一种或多种亲水性或疏水性聚合物。
(b)可消化的、长链(C8-C50、特别是C12-C40)、取代或未取代的烃类如脂肪酸、脂肪醇、脂肪酸甘油酯、矿物和植物油及蜡。熔点为25-90℃的烃类是优选的。在这些长链烃物质中,脂肪(脂族)醇是优选的。该制剂通常可含有最多达60%(重量)的至少一种可消化的长链烃。
(c)聚二醇。该制剂适于含有最多达60%(重量)的一种或多种聚二醇。
一种特别适宜的控制释放基质包含一种或多种烷基纤维素和一种或多种C12-C36脂族醇。烷基纤维素优选C1-C6烷基纤维素,特别是乙基纤维素。本发明的控制释放制剂优选含有1-20%(重量)、特别是2-15%(重量)的一种或多种烷基纤维素。
脂族醇一般可以是月桂醇、肉豆蔻醇或硬脂醇,但是优选为鲸蜡醇,或更优选鲸蜡醇硬脂醇混合物(cetostearyl alcohol)。该控制释放制剂适于含有5-30%(重量)脂族醇,优选10-25%(重量)脂族醇。
该控制释放基质还可任选含有药物领域中常用的其他可药用成分,例如稀释剂、润滑剂、粘合剂、制粒助剂、着色剂、调味剂、表面活性剂、pH调节剂、抗粘连剂和滑动剂(glidants),如癸二酸二丁酯、氢氧化铵、油酸和胶体二氧化硅。
本发明的控制释放制剂通常可以用药物领域中常用的任何膜包衣材料进行膜包衣。优选使用含水膜包衣。
或者,本发明的控制释放制剂可以包含具有控制释放包衣的正常释放基质。优选该制剂包含含有活性成分和成球剂的膜包衣球剂。
成球剂可以是可与活性成分团成球以形成球剂的任何适宜的可药用物质。优选的成球剂是微晶纤维素。所用微晶纤维素可以是例如Avicel PH 101 或 Avicel PH 102(商标,FMC Corporation)。
所述球剂可任选含有药物领域常用的其他可药用成分,例如粘合剂、填充剂和着色剂。适宜的粘合剂包括水溶性聚合物、水溶性羟烷基纤维素如羟丙基纤维素或水不溶性聚合物(它也可以具有控制释放性质)如丙烯酸聚合物或共聚物例如乙基纤维素。适宜的填充剂包括乳糖。
所述球剂用一种可使活性成分在含水介质中以控制的速度释放的材料包衣。适宜的控制释放包衣材料包括水不溶性蜡和聚合物如聚甲基丙烯酸酯(例如Eudragit polymers,商标),或水不溶性纤维素,特别是乙基纤维素。可任选包括水溶性聚合物如聚乙烯吡咯烷酮或水溶性纤维素如羟丙基甲基纤维素或羟丙基纤维素。可以任选加入其他水溶性试剂如多乙氧基醚。
或者可以将药物包覆成惰性non-pareil小丸,并且用可使活性成分向含水介质中控制释放的物质包覆该装有药物的小丸。
另一方面,本发明提供了制备本发明控制释放制剂的方法,该方法包含在控制释放基质中掺入反胺苯环醇或其可药用盐,例如:
(a)将包含反胺苯环醇或其可药用盐以及一种或多种烷基纤维素的混合物制粒;
(b)将含有烷基纤维素的颗粒与一种或多种C12-36脂族醇混合;以及任选
(c)使颗粒成型并压制颗粒,并且如果需要,进行膜包衣;或者
(d)将包含反胺苯环醇或其可药用盐、乳糖和一种或多种烷基纤维素以及一种或多种C12-36脂族醇的混合物制粒;以及任选
(e)将所述颗粒成型并压制颗粒,并且如果需要进行膜包衣。
本发明控制释放制剂也可以通过下述方法制备成膜包衣球剂:
(a)将包含反胺苯环醇或其可药用盐以及成球剂的混合物制粒;
(b)挤压制粒混合物,得到挤出物;
(c)将挤出物团成球直至形成球状体;以及
(d)用膜包衣包覆这些球状体。
本发明优选的单位剂型的形式包含装有控制释放颗粒的胶囊剂,该颗粒主要包含活性成分、疏水性易熔的载体或稀释剂,以及任选含有亲水性释放调节剂。特别是,该控制释放颗粒优选通过下述方法制备,该方法包含:使干燥的活性成分与易熔的释放控制材料形成混合物,然后在高速混合器中对混合物进行机械加工,同时输入足以使易熔材料熔融或软化的能量,以使其与活性成分形成颗粒。将所得颗粒冷却后进行适当过筛,得到大小为0.1-3.0mm、优选0.25-2.0mm的颗粒。下面描述了本发明的一个实例,它适用于剂量单位的工业化生产。
当使用该加工技术时发现,为了最容易地达到所需的释放特性(如上所讨论的体内与体外释放特性),所加工的组合物应该包含两种基本成分,即:
(a)反胺苯环醇或其盐;和
(b)疏水性易熔载体或稀释剂;以及任选
(c)释放控制成分,它包含水溶性易熔材料或可溶解颗粒或不溶解颗粒的有机或无机材料。
我们已发现,反胺苯环醇或其可药用盐在组合物中的总量可以在很宽范围内变化,例如占组合物的10-90%(重量)。
疏水性易熔成分(b)应该是疏水材料,如天然的或合成的蜡或油,例如氢化植物油、氢化蓖麻油、微晶蜡、蜂蜡、巴西棕榈蜡或一硬脂酸甘油酯,并且适合的熔点为35-140℃、优选45-110℃。
当释放调节成分(c)是水溶性易熔材料时,一般为聚乙二醇;而当其是颗粒材料时,一般为可药用材料如磷酸二钙或乳糖。
制备本发明制剂的另一优选方法包含:
(a)将颗粒形式的反胺苯环醇或其可药用盐与熔点为35-140℃的颗粒状疏水性易熔载体或稀释剂以及任选与释放控制成分(包含水溶性易熔材料或可溶解颗粒的或不溶解颗粒的有机或无机材料)的混合物,以能使载体或稀释剂熔融或软化的速度和能量输入在高速混合器中进行机械加工,使其形成附聚物;
(b)将较大的附聚物粉碎,得到控制释放种子;和
(c)继续进行机械加工,同时任选再加入低百分含量的载体或稀释剂。
(d)任选地重复步骤(c)和可能地重复步骤(b)一次或多次。
该方法能够以高产率(大于80%)得到所需大小范围的、具有所需反胺苯环醇或其盐的均匀释放速率的颗粒。
可将所得颗粒过筛,以除去任何过大或过小的物质,然后通过(例如)将其封入硬的明胶胶囊(其中含有所需剂量的活性物质)中或通过将其压成片制成所需的剂量单位。
在本发明的该方法中,优选在步骤(a)加入全部反胺苯环醇或其盐,以及所用的大部分疏水性易熔释放控制材料。在步骤(a)加入的易熔释放控制材料的量优选占在整个制备操作中加入的各成分的总量的10%-90%(W/W)、更优选20%-70%(W/W)。
该方法的步骤(a)可以在具有标准不锈钢衬里的常规高速混合器,例如Collette Vactron 75或相当的混合器中进行。对上述混合物进行加工,直到床温达到或超过约40℃,并且所得混合物具有粘结的粒状结构,在使用非聚集原料的情况下,其细度约为1-3mm至细粉。在下述实施方案中,该物质具有附聚物的外观,当其冷至40℃以下时,具有结构完整性和耐手指压碎性。在此期间,该附聚物具有不规则的大小、形状和外观。
优选使该附聚物冷却。使其冷却的温度不是严格的,一般可采用的温度在室温至37℃范围内。
采用任何适宜的方法将该附聚物粉碎,使过大的附聚物细碎,并产生粉末与小颗粒(优选直径小于2mm)的混合物。目前优选使用Jackson Crockatt成粒机采用适宜大小的筛孔,或者采用具有合适尺寸筛的Comil进行分粒。我们发现,如果在前述装置中所用的筛孔尺寸太小,则在打浆机或高速搅拌机的作用下熔融的附聚物将使筛孔堵塞,并妨碍混合物进一步通过,因而降低收率。我们发现筛孔尺寸为12是合适的。
使分粒后的物质再返回高速混合器中并继续加工。据信这将使较细的颗粒粘固,形成大小范围均匀的颗粒。
在本发明方法的一种优选形式中,继续加工分粒后的物质,直到所用的疏水性易熔材料开始软化/熔融,并且然后任选添加附加的疏水性易熔材料。继续混合,直到该混合物已被转化成所需的预定大小范围的颗粒。
为了确保在高速混合器中对各成分的能量输入均匀,优选至少部分能量以微波能的方式提供。
也可以通过其他方式传送能量,例如通过加热套或借助混合器叶轮和切碎机叶片传送。
在颗粒形成后使其冷却或静置放冷,然后可将其过筛以除去任何过大或过小的物质。
所得颗粒可以按本身已知的方法用于制备本发明的剂量单位,例如片剂或胶囊剂。
我们还发现,按照PCT申请/SE93/00225中所述的熔融法和在我们的在先未公开英国申请9324045.5(于1993年11月23日提交)中所述和要求保护的方法以及本文所述方法制备的、含有反胺苯环醇或其盐的颗粒特别适用于加工成片剂。
我们发现,通过适当选择在形成颗粒和压片中所用的物质及其所用的比例,能够在很大程度上控制反胺苯环醇或其盐从所压制的片剂中的最终溶解和释放速率。
通常,为了形成本发明的片剂,将如上所述制备的颗粒与压片赋形剂如一种或多种标准赋形剂(例如稀释剂、润滑剂、粘合剂、流动助剂、崩解剂、表面活性剂或水溶性聚合材料)掺合。
适宜的稀释剂是例如微晶纤维素、乳糖和磷酸二钙。适宜的润滑剂是例如硬脂酸镁和富马酸硬脂基酯的钠盐。适宜的粘合剂是例如羟丙基甲基纤维素、聚乙烯吡咯烷酮和甲基纤维素。
适宜的崩解剂是淀粉、淀粉甘醇酸钠、交联聚乙烯吡咯烷酮(crospovidone)和croscarmalose sodium。
适宜的表面活性剂是Poloxamer 188
、多乙氧基醚和十二烷基硫酸钠。
适宜的流动助剂是滑石、无水胶体二氧化硅。
适宜的水溶性聚合物是PEG,其分子量为1000-6000。
为了制备本发明的片剂,采用常规方法,例如采用Y-Cone或bin-blender,可将在本发明中制备的颗粒与所需赋形剂(如果有的话)混合或掺合,并且按照常规的压片方法、使用适宜尺寸的压片模将所得混合物压成片。可采用常规的压片机生产片剂,在下述实施方案中,可在标准的单冲头F3 Manesty机或Kilian RLE 15 旋转压片机上制片。
一般来说,我们发现,尽管使用这种高水溶性活性剂,如反胺苯环醇或其盐,然而按标准方法压制形成的片剂中活性成分的释放速率仍然非常低,例如相应于大于24小时、例如大于36小时期间的释放。我们发现,可以以多种方式调节释放分布图。例如,较高的药物负荷可增加释放速率;在颗粒中使用较大比例的水溶性易熔材料、或者在片剂中使用较大比例的表面活性剂也会使活性成分有较高的释放速率。通过控制这些成分的相对含量,可以调节反胺苯环醇或其盐的释放分布图。
为了使人们更充分地了解本发明,仅以说明的方式给出下列实施例。
实施例1
制备具有下列配方的片剂:
mg/片
反胺苯环醇盐酸盐 100
乳糖Ph.Eur. 68.0
纯化水Ph.Eur. 13.3*
鲸蜡醇硬脂醇混合物Ph.Eur. 42.00
(Dehydag wax 0)
硬脂酸镁Ph.Eur. 2.00
纯化的滑石Ph.Eur. 3.00
———
230.00
*在加工过程中除去。
使反胺苯环醇盐酸盐(100mg)和乳糖(68mg)成粒,将其转移到流化床成粒机上,并用乙基纤维素(15mg)和水喷雾。然后将此颗粒在60℃干燥并通过1mm筛。
向含有反胺苯环醇的温热颗粒中加入熔融的鲸蜡醇硬脂醇混合物(42mg),并将所有物质彻底混合。使该颗粒放置冷却并筛过1.6mm筛。加入纯化的滑石和硬脂酸镁,并使其与该颗粒混合。然后将此颗粒压成片。
用具有下列配方的膜包衣对所述片进行包衣。
mg/片
羟丙基甲基纤维素 0.770
(Ph.Eur.15cps (Methocel E15))
羟丙基甲基纤维素 3.87
(Ph.Eur.5cps(Methocel E5))
Opaspray M-1-7111B(33%固体) 2.57
聚乙二醇 400 USNF 0.520
纯化的滑石Ph.Eur. 0.270
纯化水Ph.Eur. 55.52*
*在加工过程中除去。
实施例2
制备具有下列配方的片剂:
mg/片
反胺苯环醇盐酸盐 100.0
乳糖Ph.Eur. 58.0
乙基纤维素USNF 15.0
(Ethocel 45CP)
鲸蜡醇硬脂醇混合物Ph.Eur. 52.0
(Dehydag wax 0)
硬脂酸镁Ph.Eur. 2.00
纯化的滑石Ph.Eur. 3.00
将反胺苯环醇盐酸盐(100mg)、乳糖(58mg)和乙基纤维素(15mg)的混合物成粒,同时加入熔融的鲸蜡醇硬脂醇混合物(52mg),并将全部物质彻底混合。使该颗粒放置冷却,并筛过1.6mm筛。加入纯化的滑石和硬脂酸镁,并将其与所述颗粒混合。然后将该颗粒压成片,用具有实施例1中所给配方的膜包衣将所述片进行包衣。
实施例3
按照实施例2中所述方法制备具有下列配方的膜包衣片剂:
mg/片
反胺苯环醇盐酸盐 100.00
乳糖Ph.Eur. 70.50
羟乙基纤维素Ph.Eur. 12.50
鲸蜡醇硬脂醇混合物Ph.Eur. 42.00
硬脂酸镁Ph.Eur. 2.00
纯化的滑石Ph.Eur. 3.00
体外溶解研究
对上述制备的片剂进行体外溶解研究。结果列于表Ⅰ中。
表Ⅰ | |||
反胺苯环醇的释放WT% | |||
时间(小时) | 实施例1 | 实施例2 | 实施例3 |
1 | 39 | 35 | 43 |
2 | 52 | 47 | 60 |
4 | 67 | 62 | 84 |
8 | 82 | 78 | 97 |
12 | 90 | 86 | - |
*对片芯进行测量
在包括12名健康志愿者的实验中,发现在服用一片实施例2的片剂后,反胺苯环醇的血清含量如图1中所说明的那样。
实施例4和5
通过下列步骤制备具有下面表Ⅱ所给配方的颗粒:
ⅰ.将成分(a)和(c)(一次投料总重量为0.7kg)装入带有变速混合及成粒叶片的10升容量的Collette Gral Mixer(或类似设备)的转筒中;
ⅱ.在约150-1000rpm条件下混合各成分,同时加热至转筒中的内含物凝聚为止。
ⅲ.使凝聚物质通过Comil和/或Jackson Crockatt使其分粒,得到控制释放种子。
ⅳ.在10升Collette Gral的转筒中温热并混合经分粒的物质,直到形成所需预定尺寸的均匀多颗粒,其产率大于80%。此过程约需5分钟。
ⅴ.从混合器中倒出该多颗粒,并使其过筛,以分离出用0.5-2mm孔径筛收集的多颗粒。
表Ⅱ | ||
实施例 | 4 | 5 |
(a)反胺苯环醇HCl(Wt%) | 50 | 75 |
(b)氢化植物油(Wt%) | 50 | 25 |
实施例6
采用Y-Cone或bin-blender将实施例4的颗粒样品与硬脂酸镁和纯化的滑石掺合。然后或者采用(1)14×6mm、(2)16×7mm 或(3)18.6×7.5mm胶囊成型工具,在单冲头F3 Manesty压片机上将所掺合的混合物压片,得到含200、300和400mg反胺苯环醇HCl的片剂。每剂量单位中各成分的含量如下:
表Ⅲ | |||
片成分 | MG/片 | ||
1 | 2 | 3 | |
反胺苯环醇盐酸盐 | 200 | 300 | 400 |
氢化植物油 | 200 | 300 | 400 |
小计 | 400 | 600 | 800 |
纯化的滑石 | 12.63 | 18.95 | 25.26 |
硬脂酸镁 | 8.42 | 12.63 | 16.84 |
通过采用Ph.Eur.Paddle Method 100 rpm、0.1N HCl进行溶解,对各片进行评价。
用改进的Ph.Eur.Basket代替Ph.Eur.Paddle,以评价未压制的颗粒。
结果示于下列表Ⅳ中:
这些结果证实了压片在降低释放速率方面的效力。
实施例7
采用与实施例3类似的方法,然后将实施例5的颗粒样品压片,每单位剂量中各成分的含量为:
表Ⅴ | |||
片成分 | MG/片 | ||
4 | 5 | 6 | |
反胺苯环醇盐酸盐 | 200 | 300 | 400 |
氢化植物油 | 66.7 | 100 | 133 |
小计 | 266.7 | 400 | 533 |
纯化的滑石 | 7.63 | 11.44 | 15.25 |
硬脂酸镁 | 5.16 | 7.63 | 10.17 |
还是通过上述的溶解方法对各片剂及未压制的多颗粒样品(每一样品含400mg反胺苯环醇盐酸盐)进行评价。所得结果列于下面表Ⅵ中:
这些结果表明,通过增加高水溶性反胺苯环醇盐酸盐的负荷(在此实施例中为75%W/W,与在实施例6中50%W/W的负荷相比较)可以实现活性成分的释放速率的显著加快。
实施例8
重复实施例4,所不同的是采用下列配方:
反胺苯环醇HCl 200mg/片
氢化植物油 163.0mg/片
如实施例6所述,将所得多颗粒与下列成分掺合:
纯化的滑石 11.5mg/片
硬脂酸镁 7.66mg/片
如实施例6所述,将掺合物压片,所不同的是使用15mm×6.5mm正常凹的胶囊成型平面/平面冲头。
通过上述溶解方法评价所得的片剂。所得结果示于表Ⅶ中:
表Ⅶ
试验开始后的小时数 | 反胺苯环醇盐酸盐的释放% |
1 | 20 |
2 | 27 |
3 | 32 |
4 | 37 |
6 | 44 |
8 | 50 |
10 | 55 |
12 | 60 |
16 | 67 |
20 | 73 |
24 | 77 |
在包括5名健康男性志愿者的实验中,由单剂量给药上述片剂与给药市售的反胺苯环醇滴剂100mg比较,所得血浆分布图如图2所示。
Claims (32)
1、用于口服给药的包含反胺苯环醇或其可药用盐的控制释放制剂。
2、权利要求1中要求保护的控制释放制剂,该制剂含有50至800mg反胺苯环醇(以反胺苯环醇盐酸盐计)。
3、权利要求1或2中要求保护的控制释放制剂,该制剂具有下述体外溶解速率(按本文所述方法测量):
4、权利要求1或2中要求保护的控制释放制剂,该制剂具有下述体外溶解速率(按本文所述方法测量):
5、权利要求1或2中要求保护的控制释放制剂,该制剂具有下述体外溶解速率(按本文所述方法测量):
6、权利要求1或2中要求保护的控制释放制剂,该制剂具有下述体外溶解速率(按本文所述方法测量):
7、按照权利要求1至6中任何一项的固态控制释放口服剂型,该剂型包含在口服给药后在适于提供反胺苯环醇或其盐的控制释放的基质中的治疗有效量的反胺苯环醇或其盐。
8、按照权利要求1至7中任何一项的剂型,其特征在于所述基质包含一种控制释放基质,后者包含至少一种烷基(优选C1-C6烷基)纤维素、至少一种C12-C36(优选C14-C22)脂族醇,以及任选至少一种聚二醇、优选聚乙二醇。
9、按照权利要求8的剂型,其特征在于至少一种烷基纤维素是乙基纤维素。
10、按照权利要求8或9的剂型,其特征在于该剂型含有1至20%W/W,优选2至15%W/W的一种或多种烷基纤维素。
11、按照权利要求8至10中任何一项的剂型,其特征在于脂族醇包含月桂醇、肉豆蔻醇、硬脂醇、或者优选鲸蜡醇或鲸蜡醇硬脂醇混合物。
12、按照权利要求8至11中任何一项的剂型,其特征在于该剂型含有5至30%W/W的脂族醇,优选10至25%W/W的脂族醇。
13、按照权利要求1至6中任何一项的以膜包衣球剂形式存在的剂型,其特征在于球剂基质包含成球剂,优选微晶纤维素。
14、按照权利要求1至6中任何一项的以多颗粒剂形式存在的剂型,其中所述基质包含熔点为35-140℃的疏水性易熔载体或稀释剂,并任选包含释放控制成分,该释放控制成分包含水溶性易熔材料或可溶解颗粒的或不溶解颗粒的有机或无机材料。
15、按照权利要求1至6中任何一项的剂型,该剂型包含通过压制权利要求14的多颗粒而形成的片剂。
16、一种固态控制释放口服剂型的制备方法,其特征在于在口服给药后,在适于提供反胺苯环醇或其盐的控制释放的基质中掺入治疗有效量的反胺苯环醇或其盐。
17、按照权利要求16的方法,其中在所述剂型中掺入50至800mg反胺苯环醇(以反胺苯环醇盐酸盐计)。
18、按照权利要求16或17的方法,其中溶解速率(按本文所述方法测量)如下:
19、按照权利要求16或17的方法,其中溶解速率(按本文所述方法测量)如下:
20、按照权利要求16或17的方法,其中溶解速率(按本文所述方法测量)如下:
21、按照权利要求16或17的方法,其中溶解速率(按本文所述方法测量)如下:
22、按照权利要求16至21中任何一项的方法,其特征在于所述基质包含控制释放基质,后者包含至少一种烷基(优选C1至C6烷基)纤维素、至少一种C12至C36(优选C14至C22)脂族醇,以及任选至少一种聚二醇,优选聚乙二醇。
23、按照权利要求16至22中任何一项的方法,其特征在于至少一种烷基纤维素是乙基纤维素。
24、按照权利要求16至23中的任何一项的方法,其特征在于所述剂型含有1至20%W/W,优选2至15%W/W的一种或多种烷基纤维素。
25、按照权利要求16至24中任何一项的方法,其特征在于所述脂族醇包含月桂醇、肉豆蔻醇、硬脂醇,或者优选鲸蜡醇或鲸蜡醇硬脂醇混合物。
26、按照权利要求16至25中任何一项的方法,其特征在于所述剂型含有5至30%W/W的脂族醇,优选10至25%W/W的脂族醇。
27、按照权利要求16至26中任何一项的方法,其特征在于:
(a)将包含反胺苯环醇或其可药用盐以及一种或多种烷基纤维素的混合物制粒;
(b)将含有烷基纤维素的颗粒与一种或多种C12-36脂族醇混合;以及任选
(c)使颗粒成型并压制颗粒,并且如果需要,进行膜包衣。
28、按照权利要求16至26中任何一项的方法,其特征在于:
(a)将包含反胺苯环醇或其可药用盐、乳糖和一种或多种烷基纤维素以及一种或多种C12-36脂族醇的混合物制粒;以及任选
(b)将所述颗粒成型并压制颗粒,并且进行膜包衣。
29、按照权利要求16至21中任何一项的方法,其特征在于:
(a)将包含反胺苯环醇或其可药用盐以及成球剂的混合物制粒;
(b)挤压制粒混合物,得到挤出物;
(c)将挤出物团成球直至形成球状体;以及
(d)用膜包衣包覆这些球状体。
30、按照权利要求16至21中任何一项的方法,其特征在于:
(a)将颗粒形式的反胺苯环醇或其可药用盐与熔点为35-140℃的颗粒状疏水性易熔载体或稀释剂以及任选与释放控制成分(包含水溶性易熔材料或可溶解颗粒的或不溶解颗粒的有机或无机材料)的混合物,以能使载体或稀释剂熔融或软化的速度和能量输入在高速混合器中进行机械加工,使其形成附聚物;
(b)将较大的附聚物粉碎,得到控制释放种子;和
(c)继续进行机械加工,同时任选再加入低百分含量的载体或稀释剂。
(d)任选地重复步骤(c)和可能地重复步骤(b)一次或多次。
31、按照权利要求16至21中任何一项的方法,其特征在于:使干燥的活性成分与易熔的释放控制材料形成药物混合物,然后在高速混合器中对混合物进行机械加工,同时输入足以使易熔材料熔融或软化的能量,以使其与活性成分形成颗粒。
32、按照权利要求16至21中任何一项的方法,该方法包含压制通过权利要求15或16的方法获得的颗粒。
Applications Claiming Priority (8)
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DE4315525A DE4315525B4 (de) | 1993-05-10 | 1993-05-10 | Pharmazeutische Zusammensetzung |
DEP4315525.1 | 1993-05-10 | ||
GB9324045A GB2284760B (en) | 1993-11-23 | 1993-11-23 | A method of preparing pharmaceutical compositions by melt pelletisation |
GB9324045.5 | 1993-11-23 | ||
GB9404544.0 | 1994-03-09 | ||
GB9404544A GB9404544D0 (en) | 1994-03-09 | 1994-03-09 | Controlled release formulation |
GB9404928A GB2287880A (en) | 1994-03-14 | 1994-03-14 | Production of sustained release compositions |
GB9404928.5 | 1994-03-14 |
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CNB991066421A Division CN1146410C (zh) | 1993-05-10 | 1999-05-17 | 控制释放制剂 |
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CN1094755C CN1094755C (zh) | 2002-11-27 |
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CN94105356A Expired - Lifetime CN1094755C (zh) | 1993-05-10 | 1994-05-10 | 含反胺苯环醇或其盐的控制释放制剂 |
CNB991066421A Expired - Lifetime CN1146410C (zh) | 1993-05-10 | 1999-05-17 | 控制释放制剂 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100411611C (zh) * | 2002-04-05 | 2008-08-20 | 欧洲凯尔蒂克公司 | 用于持续,不变且独立释放活性化合物的基质 |
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 |
US7968120B2 (en) | 2001-09-28 | 2011-06-28 | Mcneil-Ppc, Inc. | Modified release dosage forms |
US8673352B2 (en) | 2005-04-15 | 2014-03-18 | Mcneil-Ppc, Inc. | Modified release dosage form |
Families Citing this family (194)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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 |
NZ260408A (en) * | 1993-05-10 | 1996-05-28 | Euro Celtique Sa | Controlled release preparation comprising tramadol |
DE4329794C2 (de) * | 1993-09-03 | 1997-09-18 | Gruenenthal Gmbh | Tramadolsalz enthaltende Arzneimittel mit verzögerter Wirkstofffreisetzung |
KR100354702B1 (ko) | 1993-11-23 | 2002-12-28 | 유로-셀티크 소시에떼 아노뉨 | 약학조성물의제조방법및서방형조성물 |
US5891471A (en) | 1993-11-23 | 1999-04-06 | Euro-Celtique, S.A. | Pharmaceutical multiparticulates |
US5843480A (en) | 1994-03-14 | 1998-12-01 | Euro-Celtique, S.A. | Controlled release diamorphine formulation |
GB9422154D0 (en) | 1994-11-03 | 1994-12-21 | Euro Celtique Sa | Pharmaceutical compositions and method of producing the same |
US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
US5698210A (en) * | 1995-03-17 | 1997-12-16 | Lee County Mosquito Control District | Controlled delivery compositions and processes for treating organisms in a column of water or on land |
US5912268A (en) * | 1995-05-22 | 1999-06-15 | Alza Corporation | Dosage form and method for treating incontinence |
US6262115B1 (en) * | 1995-05-22 | 2001-07-17 | Alza Coporation | Method for the management of incontinence |
GB9519363D0 (en) * | 1995-09-22 | 1995-11-22 | Euro Celtique Sa | Pharmaceutical formulation |
EP0969818B1 (en) * | 1997-03-11 | 2004-09-08 | Arakis Ltd. | Dosage forms comprising separate portions of r- and s-enantiomers |
DE19710008A1 (de) * | 1997-03-12 | 1998-09-17 | Basf Ag | Feste, mindestens zweiphasige Zubereitungsformen eines Opioid-Analgeticums mit verzögerter Freisetzung |
US6635280B2 (en) | 1997-06-06 | 2003-10-21 | Depomed, Inc. | Extending the duration of drug release within the stomach during the fed mode |
JP4083818B2 (ja) | 1997-06-06 | 2008-04-30 | ディポメド,インコーポレイティド | 高度可溶性薬物の制御された放出のための胃滞留性の経口薬物投与形 |
WO1999001111A1 (en) * | 1997-07-02 | 1999-01-14 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
DE19729487A1 (de) * | 1997-07-10 | 1999-01-14 | Dresden Arzneimittel | Verfahren zur Herstellung von Wirkstoff-Zubereitungen mit kontrollierter Freisetzung aus einer Matrix |
TR200001828T2 (tr) * | 1997-12-22 | 2000-11-21 | Euro-Celtique, S.A. | Opioid dozaj şekillerinin kötüye kullanımını önlemeye yönelik bir yöntem. |
US6375957B1 (en) | 1997-12-22 | 2002-04-23 | Euro-Celtique, S.A. | Opioid agonist/opioid antagonist/acetaminophen combinations |
ES2415876T3 (es) | 1997-12-22 | 2013-07-29 | Euro-Celtique S.A. | Forma de dosificación farmacéutica oral que comprende una combinación de un agonista de opiáceos y un antagonista de opiáceos |
JP4367722B2 (ja) * | 1998-04-17 | 2009-11-18 | 大正製薬株式会社 | マルチプルユニットタイプ徐放性錠剤 |
CN1148171C (zh) * | 1998-04-17 | 2004-05-05 | 大正制药株式会社 | 多单元缓释片剂 |
US6156342A (en) * | 1998-05-26 | 2000-12-05 | Andex Pharmaceuticals, Inc. | Controlled release oral dosage form |
US20060128806A1 (en) * | 1998-05-28 | 2006-06-15 | Medical Research Institute | Controlled release arginine alpha-ketoglutarate |
US6264974B1 (en) | 1998-07-07 | 2001-07-24 | Salvagnini Italia Spa | Buccal and sublingual administration of physostigmine |
DE29818454U1 (de) * | 1998-10-15 | 1999-01-14 | Euro Celtique Sa | Opioid-Analgetikum |
US6806294B2 (en) | 1998-10-15 | 2004-10-19 | Euro-Celtique S.A. | Opioid analgesic |
AU3469100A (en) * | 1999-01-05 | 2000-07-24 | Copley Pharmaceutical Inc. | Sustained release formulation with reduced moisture sensitivity |
DE19918325A1 (de) | 1999-04-22 | 2000-10-26 | Euro Celtique Sa | Verfahren zur Herstellung von Arzneiformen mit regulierter Wirkstofffreisetzung mittels Extrusion |
CA2388560A1 (en) * | 1999-08-31 | 2001-03-08 | Grunenthal Gmbh | Sustained-release form of administration containing tramadol saccharinate |
SK285128B6 (sk) | 1999-12-28 | 2006-07-07 | Zentiva, A. S. | Liečivý prípravok s riadeným uvoľňovaním obsahujúci tramadol hydrochlorid a spôsob jeho prípravy |
CN101703777B (zh) | 2000-02-08 | 2012-11-28 | 欧罗赛铁克股份有限公司 | 抗破坏口服阿片样激动剂 |
US6544555B2 (en) | 2000-02-24 | 2003-04-08 | Advancis Pharmaceutical Corp. | Antibiotic product, use and formulation thereof |
DE60107393T2 (de) | 2000-03-01 | 2005-12-01 | Euro-Celtique S.A. | Verwendung von tramadol zur herstellung eines arzneimittels zur behandlung von funktionelle gastrointestinale krankenheiten |
EP1322303A1 (en) * | 2000-10-03 | 2003-07-02 | Penwest Pharmaceuticals Co. | Delivery system for multi-pharmaceutical active materials at various release rates |
US20020068078A1 (en) | 2000-10-13 | 2002-06-06 | Rudnic Edward M. | Antifungal product, use and formulation thereof |
DE10108122A1 (de) | 2001-02-21 | 2002-10-02 | Gruenenthal Gmbh | Arzneimittel auf Basis von Tramadol |
WO2002074241A2 (en) | 2001-03-16 | 2002-09-26 | Dmi Biosciences Inc. | Method of delaying ejaculation |
US7858118B2 (en) * | 2001-04-11 | 2010-12-28 | Galephar Pharmaceutical Research, Inc. | Extended release composition containing Tramadol |
EP1387673B1 (en) | 2001-05-11 | 2010-12-29 | Endo Pharmaceuticals Inc. | Abuse-resistant controlled-release opioid dosage form |
US7052706B2 (en) * | 2001-06-08 | 2006-05-30 | Nostrum Pharmaceuticals, Inc. | Control release formulation containing a hydrophobic material as the sustained release agent |
WO2003002100A1 (en) * | 2001-06-26 | 2003-01-09 | Farrell John J | Tamper-proof narcotic delivery system |
PT1416842E (pt) * | 2001-07-18 | 2009-03-31 | Euro Celtique Sa | Composições farmacêuticas de oxicodona e naloxona |
KR20040029405A (ko) | 2001-08-06 | 2004-04-06 | 유로-셀티크 소시에떼 아노뉨 | 방출성 및 격리된 길항제와 오피오이드 효능제의 제제 |
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 |
US6479060B1 (en) * | 2001-09-04 | 2002-11-12 | Healthpoint, Ltd. | Elegant hydrogenated castor oil ointments |
PE20030527A1 (es) | 2001-10-24 | 2003-07-26 | Gruenenthal Chemie | Formulacion farmaceutica con liberacion retardada que contiene 3-(3-dimetilamino-1-etil-2-metil-propil) fenol o una sal farmaceuticamente aceptable del mismo y tabletas para administracion oral que la contienen |
US7612112B2 (en) | 2001-10-25 | 2009-11-03 | Depomed, Inc. | Methods of treatment using a gastric retained gabapentin dosage |
TWI312285B (en) | 2001-10-25 | 2009-07-21 | Depomed Inc | Methods of treatment using a gastric retained gabapentin dosage |
US20060159743A1 (en) * | 2001-10-25 | 2006-07-20 | Depomed, Inc. | Methods of treating non-nociceptive pain states with gastric retentive gabapentin |
RU2311903C2 (ru) * | 2001-11-07 | 2007-12-10 | Синтон Б.В. | Таблетки тамзулосина |
KR20030060730A (ko) * | 2002-01-09 | 2003-07-16 | 하나제약 주식회사 | 난용성 약물의 서방화 제제 조성물 |
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 |
US8128957B1 (en) | 2002-02-21 | 2012-03-06 | Valeant International (Barbados) Srl | Modified release compositions of at least one form of tramadol |
IL164077A0 (en) * | 2002-03-22 | 2005-12-18 | Cilag Ag | Sustained release formulation of tramadol |
US7125563B2 (en) * | 2002-04-12 | 2006-10-24 | Dava Pharmaceuticals, Inc. | Sustained release pharmaceutical preparations and methods for producing the same |
US7776314B2 (en) | 2002-06-17 | 2010-08-17 | Grunenthal Gmbh | Abuse-proofed dosage system |
CN1662223A (zh) * | 2002-06-27 | 2005-08-31 | 西拉格股份公司 | 含水溶性活性成分的球形微丸 |
WO2004026256A2 (en) * | 2002-09-20 | 2004-04-01 | Alpharma, Inc. | Sustained-release opioid formulations and methods of use |
US7815934B2 (en) | 2002-09-20 | 2010-10-19 | Alpharma Pharmaceuticals, Llc | Sequestering subunit and related compositions and methods |
WO2004026262A2 (en) * | 2002-09-23 | 2004-04-01 | Verion, Inc. | Abuse-resistant pharmaceutical compositions |
TWI319713B (en) | 2002-10-25 | 2010-01-21 | Sustained-release tramadol formulations with 24-hour efficacy | |
ATE400819T1 (de) * | 2002-10-25 | 2008-07-15 | Labopharm Inc | Zubereitungen mit kontrollierter freisetzung |
AR045972A1 (es) * | 2002-10-25 | 2005-11-23 | Labopharm Inc | Formulaciones de tramadol de liberacion sostenida con eficacia de 24 horas |
US8487002B2 (en) * | 2002-10-25 | 2013-07-16 | Paladin Labs Inc. | Controlled-release compositions |
US20040086566A1 (en) * | 2002-11-04 | 2004-05-06 | Alpharma, Inc. | Waxy matrix dosage forms |
JP2006514986A (ja) * | 2002-12-13 | 2006-05-18 | シラグ・アクチエンゲゼルシヤフト | トラマドールおよびトピラメートを含んでなる制御放出調製物 |
DE10300325A1 (de) | 2003-01-09 | 2004-07-22 | Hexal Ag | Granulat mit öliger Substanz, Herstellungsverfahren und Tablette |
KR100712356B1 (ko) * | 2003-01-23 | 2007-05-02 | (주)아모레퍼시픽 | 서방성 제제 및 그의 제조방법 |
US7413749B2 (en) * | 2003-03-11 | 2008-08-19 | Purdue Pharma L.P. | Titration dosing regimen for controlled release tramadol |
EP1905435A3 (en) | 2003-03-11 | 2008-05-14 | Euro-Celtique S.A. | 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 |
MY135852A (en) | 2003-04-21 | 2008-07-31 | Euro Celtique Sa | Pharmaceutical products |
US8790689B2 (en) * | 2003-04-30 | 2014-07-29 | Purdue Pharma L.P. | Tamper resistant transdermal dosage form |
EP2316440A1 (en) | 2003-04-30 | 2011-05-04 | Purdue Pharma L.P. | Transdermal dosage form comprising an active agent component and an adverse agent component at the distal site of the active agent layer and one fluid communication between the surface of the active agent and the adverse agent |
DE102004020220A1 (de) * | 2004-04-22 | 2005-11-10 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen 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 |
DE10361596A1 (de) * | 2003-12-24 | 2005-09-29 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
DE102005005446A1 (de) | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Bruchfeste Darreichungsformen mit retardierter Freisetzung |
DE102004032051A1 (de) | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten, festen Darreichungsform |
DE10336400A1 (de) | 2003-08-06 | 2005-03-24 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
US20090304793A1 (en) * | 2003-09-22 | 2009-12-10 | Alpharma, Inc. | Sustained release opioid formulations and methods of use |
US20060172006A1 (en) * | 2003-10-10 | 2006-08-03 | Vincent Lenaerts | Sustained-release tramadol formulations with 24-hour clinical efficacy |
GB0501638D0 (en) * | 2005-01-28 | 2005-03-02 | Euro Celtique Sa | Particulates |
EP1604667A1 (en) * | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the restless leg syndrome |
EP1604666A1 (en) | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD) |
AU2005259961B2 (en) * | 2004-06-25 | 2012-05-17 | Board Of Regents, The University Of Texas System | Methods and compositions for the treatment of attention deficit hyperactivity disorder and hyperphenylalanemia |
DE102004032049A1 (de) * | 2004-07-01 | 2006-01-19 | Grünenthal GmbH | Gegen Missbrauch gesicherte, orale Darreichungsform |
WO2006009403A1 (en) * | 2004-07-22 | 2006-01-26 | Amorepacific Corporation | Sustained-release preparations containing topiramate and the producing method thereof |
CN101132772B (zh) * | 2005-01-28 | 2012-05-09 | 欧洲凯尔特公司 | 耐醇剂型 |
KR20070115918A (ko) * | 2005-01-31 | 2007-12-06 | 교린 세이야꾸 가부시키 가이샤 | 멀티플 유닛형 경구 서방성 제제 및 그 제조방법 |
BG66008B1 (bg) * | 2005-02-01 | 2010-10-29 | Cooperative Clinical Drug Research And Development Ag | Лекарствен препарат с изменено освобождаване |
DE102005005449A1 (de) * | 2005-02-04 | 2006-08-10 | Grünenthal GmbH | Verfahren zur Herstellung einer gegen Missbrauch gesicherten Darreichungsform |
EP1702558A1 (en) | 2005-02-28 | 2006-09-20 | Euro-Celtique S.A. | Method and device for the assessment of bowel function |
EP1695700A1 (en) * | 2005-02-28 | 2006-08-30 | Euro-Celtique S.A. | Dosage form containing oxycodone and naloxone |
JP5095615B2 (ja) | 2005-06-27 | 2012-12-12 | バリアント・インターナショナル・(バルバドス)・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ | ブプロピオン塩の放出調整製剤 |
AU2006269225B2 (en) * | 2005-07-07 | 2011-10-06 | Farnam Companies, Inc. | Sustained release pharmaceutical compositions for highly water soluble drugs |
ES2620293T3 (es) | 2005-09-09 | 2017-06-28 | Paladin Labs Inc. | Composición de liberación sostenida de fármacos |
US8329744B2 (en) * | 2005-11-02 | 2012-12-11 | Relmada Therapeutics, Inc. | Methods of preventing the serotonin syndrome and compositions for use thereof |
US20090082466A1 (en) * | 2006-01-27 | 2009-03-26 | Najib Babul | Abuse Resistant and Extended Release Formulations and Method of Use Thereof |
WO2008134071A1 (en) * | 2007-04-26 | 2008-11-06 | Theraquest Biosciences, Inc. | Multimodal abuse resistant extended release formulations |
US20090176882A1 (en) | 2008-12-09 | 2009-07-09 | Depomed, Inc. | Gastric retentive gabapentin dosage forms and methods for using same |
US20070190141A1 (en) * | 2006-02-16 | 2007-08-16 | Aaron Dely | Extended release opiate composition |
ES2378573T3 (es) | 2006-03-16 | 2012-04-16 | Tris Pharma, Inc. | Formulaciones de liberación modificada que contienen complejos de fármaco-resina de intercambio iónico |
US8367107B2 (en) * | 2006-03-30 | 2013-02-05 | Nippon Zoki Pharmaceutical Co., Ltd. | Solid pharmaceutical preparation |
US20070264335A1 (en) * | 2006-05-09 | 2007-11-15 | Sherman Bernard C | Modified release tablets comprising tramadol |
HUE032156T2 (en) * | 2006-06-19 | 2017-09-28 | Alpharma Pharmaceuticals Llc | Pharmaceutical preparations |
US20080075771A1 (en) * | 2006-07-21 | 2008-03-27 | Vaughn Jason M | Hydrophilic opioid abuse deterrent delivery system using opioid antagonists |
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 |
KR20090121315A (ko) | 2007-02-12 | 2009-11-25 | 디엠아이 바이오사이언시스 인코포레이티드 | 조루 및 발기부전을 동시에 치료하는 방법 |
BRPI0807281A2 (pt) * | 2007-02-12 | 2014-04-29 | Dmi Biosciences Inc | Reduzindo os efeitos colaterais de tramadol |
JP5452236B2 (ja) * | 2007-03-02 | 2014-03-26 | ファーナム・カンパニーズ・インコーポレーテッド | ロウ様物質を用いた徐放性組成物 |
DE102007011485A1 (de) | 2007-03-07 | 2008-09-11 | Grünenthal GmbH | Darreichungsform mit erschwertem Missbrauch |
US20080031950A1 (en) * | 2007-04-27 | 2008-02-07 | Nectid Inc. | Novel anelgesic combination |
US20080026054A1 (en) * | 2007-04-27 | 2008-01-31 | Nectid Inc. | Novel anelgesic combination |
US20090028873A1 (en) * | 2007-07-27 | 2009-01-29 | Auspex Pharmaceuticals, Inc. | Substituted cyclohexanols |
CZ300468B6 (cs) * | 2007-09-20 | 2009-05-27 | Zentiva, A. S | Léková forma obsahující tramadol s kontrolovaným uvolnováním po dobu 24 hodin a zpusob její prípravy |
US20090081291A1 (en) * | 2007-09-26 | 2009-03-26 | Gin Jerry B | Sustained Release Dosage Forms For Delivery of Agents to an Oral Cavity of a User |
KR20100069685A (ko) * | 2007-10-16 | 2010-06-24 | 라보팜 인코포레이트 | 아세트아미노펜과 트라마돌의 지속 방출을 위한 이중층 조성물 |
WO2009088673A2 (en) * | 2007-12-17 | 2009-07-16 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
US20100151014A1 (en) * | 2008-12-16 | 2010-06-17 | Alpharma Pharmaceuticals, Llc | Pharmaceutical composition |
BRPI0821732A2 (pt) | 2007-12-17 | 2015-06-16 | Labopharm Inc | Formulações de liberação controlada , forma de dosagem sólida, e, uso da formulação de liberação controlada |
US8623418B2 (en) * | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
JP5774853B2 (ja) | 2008-01-25 | 2015-09-09 | 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 | 医薬投薬形 |
US20090246276A1 (en) | 2008-01-28 | 2009-10-01 | Graham Jackson | Pharmaceutical Compositions |
CA2720108C (en) * | 2008-03-11 | 2016-06-07 | Depomed, Inc. | Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic |
US8372432B2 (en) * | 2008-03-11 | 2013-02-12 | Depomed, Inc. | Gastric retentive extended-release dosage forms comprising combinations of a non-opioid analgesic and an opioid analgesic |
EP2273983B1 (en) | 2008-05-09 | 2016-07-20 | Grünenthal GmbH | Process for the preparation of an intermediate powder formulation and a final solid dosage form under usage of a spray congealing step |
GB0811024D0 (en) * | 2008-06-17 | 2008-07-23 | E Therapeutics Plc | Sustained release treatment of depression |
US20100003322A1 (en) * | 2008-07-03 | 2010-01-07 | Lai Felix S | Enteric coated hydrophobic matrix formulation |
CA2730211C (en) * | 2008-07-07 | 2016-11-08 | Euro-Celtique S.A. | Use of opioid antagonists for treating urinary retention |
US8343524B2 (en) | 2008-07-31 | 2013-01-01 | Clarke Mosquito Control Products, Inc. | Extended release tablet and method for making and using same |
EP2367541B1 (en) | 2008-12-16 | 2014-07-16 | Paladin Labs Inc. | Misuse preventative, controlled release 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 |
WO2010100657A2 (en) * | 2009-03-04 | 2010-09-10 | Fdc Limited | A novel oral controlled release dosage forms for water soluble drugs |
MX347106B (es) | 2009-03-10 | 2017-04-12 | Euro-Celtique S A * | Coposiciones farmacéuticas de liberación inmediata que comprenden oxicodona y naloxona. |
US8811578B2 (en) * | 2009-03-23 | 2014-08-19 | Telemanager Technologies, Inc. | System and method for providing local interactive voice response services |
DE102009019268A1 (de) * | 2009-04-28 | 2010-11-11 | Lts Lohmann Therapie-Systeme Ag | Arzneimittel mit poröser Matrix |
ES2560210T3 (es) | 2009-07-22 | 2016-02-17 | Grünenthal GmbH | Forma de dosificación resistente a la manipulación para opiádes sensibles a la oxidación |
JP5667183B2 (ja) | 2009-07-22 | 2015-02-12 | 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 | 加熱溶融押出成型した制御放出性投与剤型 |
WO2011026125A2 (en) * | 2009-08-31 | 2011-03-03 | Depomed, Inc. | Gastric retentive pharmaceutical compositions for immediate and extended release of acetaminophen |
US20110104272A1 (en) * | 2009-11-05 | 2011-05-05 | Depomed, Inc. | Gastric retentive extended-release dosage forms comprising combinations of acetaminophen and phenylephrine |
US9198861B2 (en) | 2009-12-22 | 2015-12-01 | Mallinckrodt Llc | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
US8597681B2 (en) | 2009-12-22 | 2013-12-03 | Mallinckrodt Llc | Methods of producing stabilized solid dosage pharmaceutical compositions containing morphinans |
ES2606227T3 (es) * | 2010-02-03 | 2017-03-23 | Grünenthal GmbH | Preparación de una composición farmacéutica en polvo mediante una extrusora |
EP2371356B1 (en) * | 2010-03-12 | 2012-12-19 | Phoeme GmbH | Multi-particle pharmaceutical formulation for colon absorption |
US20120009261A1 (en) | 2010-07-06 | 2012-01-12 | Grünenthal GmbH | Novel gastro-retentive dosage forms |
KR20130137627A (ko) | 2010-09-02 | 2013-12-17 | 그뤼넨탈 게엠베하 | 음이온성 중합체를 포함하는 내변조성 투여형 |
RU2604676C2 (ru) | 2010-09-02 | 2016-12-10 | Грюненталь Гмбх | Устойчивая к разрушению лекарственная форма, содержащая неорганическую соль |
US8623409B1 (en) | 2010-10-20 | 2014-01-07 | Tris Pharma Inc. | Clonidine formulation |
EP3272342B1 (en) | 2011-03-23 | 2021-05-26 | Ironshore Pharmaceuticals & Development, Inc. | Methods and compositions for treatment of attention deficit disorder |
US8927010B2 (en) | 2011-03-23 | 2015-01-06 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US8916588B2 (en) | 2011-03-23 | 2014-12-23 | Ironshore Pharmaceuticals & Development, Inc. | Methods for treatment of attention deficit hyperactivity disorder |
US9498447B2 (en) | 2011-03-23 | 2016-11-22 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US10905652B2 (en) | 2011-03-23 | 2021-02-02 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US10292937B2 (en) | 2011-03-23 | 2019-05-21 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
US9603809B2 (en) | 2011-03-23 | 2017-03-28 | Ironshore Pharmaceuticals & Development, Inc. | Methods of treatment of attention deficit hyperactivity disorder |
US9283214B2 (en) | 2011-03-23 | 2016-03-15 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US11241391B2 (en) | 2011-03-23 | 2022-02-08 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US9119809B2 (en) | 2011-03-23 | 2015-09-01 | Ironshore Pharmaceuticals & Development, Inc. | Compositions for treatment of attention deficit hyperactivity disorder |
US8858963B1 (en) | 2011-05-17 | 2014-10-14 | Mallinckrodt Llc | Tamper resistant composition comprising hydrocodone and acetaminophen for rapid onset and extended duration of analgesia |
US9050335B1 (en) | 2011-05-17 | 2015-06-09 | Mallinckrodt Llc | Pharmaceutical compositions for extended release of oxycodone and acetaminophen resulting in a quick onset and prolonged period of analgesia |
US8741885B1 (en) | 2011-05-17 | 2014-06-03 | Mallinckrodt Llc | Gastric retentive extended release pharmaceutical compositions |
US10702485B2 (en) | 2011-07-09 | 2020-07-07 | Syntrix Biosystems Inc. | Compositions and methods for overcoming resistance to tramadol |
AR087359A1 (es) | 2011-07-29 | 2014-03-19 | Gruenenthal Gmbh | Tableta a prueba de alteracion que proporciona liberacion inmediata del farmaco |
WO2013017234A1 (en) | 2011-07-29 | 2013-02-07 | Grünenthal GmbH | Tamper-resistant tablet providing immediate drug release |
MX356421B (es) | 2012-02-28 | 2018-05-29 | Gruenenthal Gmbh | Forma de dosificacion resistente a la manipulacion indebida que comprende un compuesto farmacologicamente activo y un polimero anionico. |
ES2692944T3 (es) | 2012-04-18 | 2018-12-05 | Grünenthal GmbH | Forma de dosificación farmacéutica resistente a la manipulación y resistente a la descarga rápida de la dosis |
US10064945B2 (en) | 2012-05-11 | 2018-09-04 | Gruenenthal Gmbh | Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc |
EP3003283A1 (en) | 2013-05-29 | 2016-04-13 | Grünenthal GmbH | Tamper resistant dosage form with bimodal release profile |
AU2014273227B2 (en) | 2013-05-29 | 2019-08-15 | Grunenthal Gmbh | Tamper-resistant dosage form containing one or more particles |
DE102013009114A1 (de) | 2013-05-29 | 2014-12-04 | Franz Gerstheimer | Pharmazeutische Zusammensetzung zur Überwindung von Metabolisierungsproblemen |
WO2014205228A1 (en) * | 2013-06-19 | 2014-12-24 | Orbis Biosciences, Inc. | Tramadol particle formulations and methods |
EA032465B1 (ru) | 2013-07-12 | 2019-05-31 | Грюненталь Гмбх | Защищенная от применения не по назначению пероральная фармацевтическая лекарственная форма, содержащая этиленвинилацетатный полимер, и способ ее изготовления |
EP3024461B1 (en) | 2013-07-23 | 2020-05-13 | Euro-Celtique S.A. | 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 |
WO2015078891A1 (en) | 2013-11-26 | 2015-06-04 | Farmaceutici Formenti S.P.A. | Preparation of a powdery pharmaceutical composition by means of cryo-milling |
CN106572980A (zh) | 2014-05-12 | 2017-04-19 | 格吕伦塔尔有限公司 | 包含他喷他多的防篡改即释胶囊制剂 |
EP3148512A1 (en) | 2014-05-26 | 2017-04-05 | Grünenthal GmbH | Multiparticles safeguarded against ethanolic dose-dumping |
KR20170139158A (ko) | 2015-04-24 | 2017-12-18 | 그뤼넨탈 게엠베하 | 즉시 방출되고 용매 추출 방지된 변조 방지된 투여 형태 |
US11590228B1 (en) | 2015-09-08 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine compositions |
CA2998259A1 (en) | 2015-09-10 | 2017-03-16 | Grunenthal Gmbh | Protecting oral overdose with abuse deterrent immediate release formulations |
CN106109431B (zh) * | 2015-12-18 | 2020-11-10 | 上海奕利制药有限公司 | 一种缓控释微丸片剂及其制备方法 |
US11590081B1 (en) | 2017-09-24 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine tablets |
AU2018360383A1 (en) | 2017-11-02 | 2020-05-21 | Natureceuticals Sdn. Bhd. | Extract of orthosiphon stamineus, formulations, and uses thereof |
WO2020086673A1 (en) * | 2018-10-26 | 2020-04-30 | Guangzhou Dazhou Biomedicine Ltd. | Ketamine oral transmucosal delivery system |
US11000488B2 (en) | 2019-03-22 | 2021-05-11 | Syntrix Biosystems Inc. | Treating pain using desmetramadol |
US11103452B2 (en) | 2019-11-08 | 2021-08-31 | Athena Bioscience, Llc | Tramadol hydrochloride solution |
US11918689B1 (en) | 2020-07-28 | 2024-03-05 | Tris Pharma Inc | Liquid clonidine extended release composition |
JP7435915B2 (ja) | 2021-07-19 | 2024-02-21 | 三菱自動車工業株式会社 | 排気還流システムの故障診断装置 |
Family Cites Families (145)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US266331A (en) * | 1882-10-24 | walmsley | ||
US2738303A (en) | 1952-07-18 | 1956-03-13 | Smith Kline French Lab | Sympathomimetic preparation |
US3065143A (en) | 1960-04-19 | 1962-11-20 | Richardson Merrell Inc | Sustained release tablet |
DE1199764B (de) | 1963-04-02 | 1965-09-02 | Gruenenthal Chemie | Verfahren zur Herstellung von basisch substituierten Phenolaethern |
US4132753A (en) * | 1965-02-12 | 1979-01-02 | American Cyanamid Company | Process for preparing oral sustained release granules |
US3830934A (en) * | 1967-07-27 | 1974-08-20 | Gruenenthal Chemie | Analgesic and antitussive compositions and methods |
US3652589A (en) * | 1967-07-27 | 1972-03-28 | Gruenenthal Chemie | 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols |
GB1405088A (en) | 1971-06-03 | 1975-09-03 | Mundipharma Ag | Slow release formulation |
FR2183546B1 (zh) | 1972-05-10 | 1975-06-20 | Servier Lab | |
US3965256A (en) | 1972-05-16 | 1976-06-22 | Synergistics | Slow release pharmaceutical compositions |
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
DE2360796B2 (de) * | 1973-12-06 | 1977-06-02 | Edelfettwerke Werner Schlüter, 2000 Hamburg; Glyco Iberica S.A., Gava, Barcelona (Spanien) Vti: Hegel, K.Th., Dr.; Dickel, K., Dipl.-Ing.; Pat.-Anwälte, 2000 Hamburg und 8000 München | Arzneimittel mit verzoegerter abgabe des wirkstoffs im darm |
US3974157A (en) * | 1974-03-04 | 1976-08-10 | Pennwalt Corporation | 1-(Amino-alkyl)-2-aryl-cyclohexane alcohols and esters |
DE2426812A1 (de) * | 1974-06-04 | 1976-01-02 | Klinge Co Chem Pharm Fab | Verfahren zur herstellung von granulaten |
GB1478759A (en) | 1974-11-18 | 1977-07-06 | Alza Corp | Process for forming outlet passageways in pills using a laser |
US4076798A (en) * | 1975-05-29 | 1978-02-28 | American Cyanamid Company | High molecular weight polyester resin, the method of making the same and the use thereof as a pharmaceutical composition |
US4063064A (en) | 1976-02-23 | 1977-12-13 | Coherent Radiation | Apparatus for tracking moving workpiece by a laser beam |
US4366172A (en) * | 1977-09-29 | 1982-12-28 | The Upjohn Company | 4-Amino-cyclohexanols, their pharmaceutical compositions and methods of use |
CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
US4259314A (en) * | 1979-12-10 | 1981-03-31 | Hans Lowey | Method and composition for the preparation of controlled long-acting pharmaceuticals |
IE49324B1 (en) | 1979-12-19 | 1985-09-18 | Euro Celtique Sa | Controlled release compositions |
JPS56140915A (en) * | 1980-04-07 | 1981-11-04 | Yamanouchi Pharmaceut Co Ltd | Pharmaceutical preparation for solid drug |
DE3024416C2 (de) * | 1980-06-28 | 1982-04-15 | Gödecke AG, 1000 Berlin | Verfahren zur Herstellung von Arzneimitteln mit retardierter Wirkstoff-Freisetzung |
JPS57171428A (en) * | 1981-04-13 | 1982-10-22 | Sankyo Co Ltd | Preparation of coated solid preparation |
DE3124983A1 (de) | 1981-06-25 | 1983-01-20 | Meditest Inst Fuer Medizinisch | Arzneiformen zur oralen verabreichung |
US4369172A (en) | 1981-12-18 | 1983-01-18 | Forest Laboratories Inc. | Prolonged release therapeutic compositions based on hydroxypropylmethylcellulose |
US4987136A (en) * | 1982-03-16 | 1991-01-22 | The Rockefeller University | Method for controlling gastrointestinal dysmotility |
US4389393A (en) | 1982-03-26 | 1983-06-21 | Forest Laboratories, Inc. | Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose |
US4421736A (en) * | 1982-05-20 | 1983-12-20 | Merrel Dow Pharmaceuticals Inc. | Sustained release diethylpropion compositions |
US4443428A (en) | 1982-06-21 | 1984-04-17 | Euroceltique, S.A. | Extended action controlled release compositions |
US4421436A (en) * | 1982-07-06 | 1983-12-20 | Texaco Development Corporation | Tension leg platform system |
ZA836627B (en) | 1982-10-08 | 1984-05-30 | Verex Lab | Constant release rate solid oral dosage formulation of pharmaceutical compounds having a high degree of water solubility |
US4917899A (en) * | 1983-12-22 | 1990-04-17 | Elan Corporation Plc | Controlled absorption diltiazem formulation |
EP0147780A3 (en) * | 1984-01-03 | 1987-03-11 | Merck & Co. Inc. | Drug delivery device |
EP0152379A3 (de) | 1984-02-15 | 1986-10-29 | Ciba-Geigy Ag | Verfahren zur Herstellung von pharmazeutischen Zusammensetzungen enthaltend unilamellare Liposomen |
GB8405112D0 (en) * | 1984-02-28 | 1984-04-04 | Akzo Nv | Anti-arrhythmic amino-alcohols |
US4894234A (en) | 1984-10-05 | 1990-01-16 | Sharma Shri C | Novel drug delivery system for antiarrhythmics |
EP0189861A3 (en) | 1985-01-26 | 1988-02-17 | Showa Denko Kabushiki Kaisha | Percutaneous absorption accelerator for ionic water-soluble medicine |
US4772475A (en) | 1985-03-08 | 1988-09-20 | Yamanouchi Pharmaceutical Co., Ltd. | Controlled-release multiple units pharmaceutical formulation |
NL8500724A (nl) * | 1985-03-13 | 1986-10-01 | Univ Groningen | Inrichtingen voor geregelde afgifte van werkzame stoffen, alsmede werkwijze ter vervaardiging daarvan. |
EP0204951B1 (en) | 1985-05-13 | 1993-01-20 | Miles Inc. | Use of calcium channel blockers in the production of compositions for withdrawal symptoms |
GB8514665D0 (en) | 1985-06-11 | 1985-07-10 | Eroceltique Sa | Oral pharmaceutical composition |
JPS61293911A (ja) * | 1985-06-24 | 1986-12-24 | Teisan Seiyaku Kk | 徐放化製剤 |
FR2585246A1 (fr) | 1985-07-26 | 1987-01-30 | Cortial | Procede d'obtention de formes pharmaceutiques solides a liberation prolongee |
GB8521350D0 (en) | 1985-08-28 | 1985-10-02 | Euro Celtique Sa | Analgesic composition |
IT1188212B (it) | 1985-12-20 | 1988-01-07 | Paolo Colombo | Sistema per il rilascio a velocita' controllata di sostanze attive |
JP2521504B2 (ja) | 1985-12-27 | 1996-08-07 | 昭和電工株式会社 | 酵素の造粒法 |
DE3602370A1 (de) | 1986-01-27 | 1987-08-06 | Chrubasik Sigrun | Verwendung von analgetica durch inhalation |
GB2186485B (en) * | 1986-02-13 | 1988-09-07 | Ethical Pharma Ltd | Slow release formulation |
DE3612212A1 (de) * | 1986-04-11 | 1987-10-15 | Basf Ag | Verfahren zur herstellung von festen pharmazeutischen formen |
US4820523A (en) | 1986-04-15 | 1989-04-11 | Warner-Lambert Company | Pharmaceutical composition |
GB8613689D0 (en) * | 1986-06-05 | 1986-07-09 | Euro Celtique Sa | Pharmaceutical composition |
GB8613688D0 (en) * | 1986-06-05 | 1986-07-09 | Euro Celtique Sa | Pharmaceutical composition |
ATE107857T1 (de) * | 1986-06-10 | 1994-07-15 | Euro Celtique Sa | Zusammensetzung mit kontrollierter freisetzung von dihydrocodein. |
DE3623193A1 (de) | 1986-07-10 | 1988-01-14 | Gruenenthal Gmbh | Neue verbindungen, diese enthaltende arzneimittel und verfahren zu deren herstellung |
US4861598A (en) | 1986-07-18 | 1989-08-29 | Euroceltique, S.A. | Controlled release bases for pharmaceuticals |
JPH0816066B2 (ja) | 1986-07-18 | 1996-02-21 | エーザイ株式会社 | 持続性薬効製剤 |
US4970075A (en) * | 1986-07-18 | 1990-11-13 | Euroceltique, S.A. | Controlled release bases for pharmaceuticals |
US4760094A (en) | 1986-10-21 | 1988-07-26 | American Home Products Corporation (Del.) | Spray dried acetaminophen |
GB8626098D0 (en) * | 1986-10-31 | 1986-12-03 | Euro Celtique Sa | Controlled release hydromorphone composition |
US5026560A (en) | 1987-01-29 | 1991-06-25 | Takeda Chemical Industries, Ltd. | Spherical granules having core and their production |
ZA882783B (en) | 1987-06-10 | 1988-10-20 | Warner-Lambert Company | Process for preparing a pharmaceutical composition |
DE3721721C1 (de) | 1987-07-01 | 1988-06-09 | Hoechst Ag | Verfahren zur Umhuellung von Granulaten |
GB8717168D0 (en) | 1987-07-21 | 1987-08-26 | Roussel Lab Ltd | Controlled-release device |
JPH01149717A (ja) * | 1987-12-04 | 1989-06-12 | Showa Denko Kk | 直腸内投与用医薬組成物 |
EP0327295A3 (en) | 1988-02-01 | 1989-09-06 | F.H. FAULDING & CO. LTD. | Tetracycline dosage form |
DE3812799A1 (de) | 1988-04-16 | 1989-10-26 | Sanol Arznei Schwarz Gmbh | Oral zu verabreichende pharmazeutische zubereitung mit kontrollierter wirkstofffreisetzung und verfahren zu deren herstellung |
US5472710A (en) | 1988-04-16 | 1995-12-05 | Schwarz Pharma Ag | Pharmaceutical preparation to be administered orally with controlled release of active substance and method for its manufacture |
JP2681373B2 (ja) | 1988-07-18 | 1997-11-26 | 塩野義製薬株式会社 | 徐放性製剤の製造法 |
US4925675A (en) * | 1988-08-19 | 1990-05-15 | Himedics, Inc. | Erythromycin microencapsulated granules |
GB8820327D0 (en) | 1988-08-26 | 1988-09-28 | May & Baker Ltd | New compositions of matter |
DE3830353A1 (de) † | 1988-09-07 | 1990-03-15 | Basf Ag | Verfahren zur kontinuierlichen herstellung von festen pharmazeutischen formen |
ATE107854T1 (de) | 1988-09-30 | 1994-07-15 | Rhone Poulenc Rorer Ltd | Pharmazeutisches granulat. |
US5178868A (en) | 1988-10-26 | 1993-01-12 | Kabi Pharmacia Aktiebolaq | Dosage form |
AU645003B2 (en) | 1988-11-08 | 1994-01-06 | Takeda Chemical Industries Ltd. | Sustained release preparations |
CA2002492A1 (en) | 1988-11-11 | 1990-05-11 | Sandra T. A. Malkowska | Pharmaceutical ion exchange resin composition |
US5196203A (en) | 1989-01-06 | 1993-03-23 | F. H. Faulding & Co. Limited | Theophylline dosage form |
CA2007055A1 (en) | 1989-01-06 | 1990-07-06 | Garth Boehm | Theophylline dosage form |
US5202128A (en) | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
CA2007181C (en) | 1989-01-06 | 1998-11-24 | Angelo Mario Morella | Sustained release pharmaceutical composition |
US5330766A (en) * | 1989-01-06 | 1994-07-19 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
FR2642420B1 (fr) | 1989-01-27 | 1991-09-06 | Valpan Sa Labo Pharma | Nouvelle forme galenique a liberation programmee contenant une association de sels ferreux, d'acide succinique et d'acide ascorbique |
US5007790A (en) | 1989-04-11 | 1991-04-16 | Depomed Systems, Inc. | Sustained-release oral drug dosage form |
US5126145A (en) | 1989-04-13 | 1992-06-30 | Upsher Smith Laboratories Inc | Controlled release tablet containing water soluble medicament |
US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
JPH0642655Y2 (ja) * | 1989-05-12 | 1994-11-09 | トミー株式会社 | フック付歯科矯正用ブラケット |
DK161743C (da) | 1989-07-03 | 1992-02-17 | Niro Atomizer As | Fremgangsmaade og apparat til agglomerering af et pulverformigt materiale |
JPH03163030A (ja) | 1989-08-28 | 1991-07-15 | Arizona Technol Dev Corp | アヘン剤活性を選択的に強化し、アヘン剤耐性と依存性を軽減するための組成物と方法 |
US5169645A (en) * | 1989-10-31 | 1992-12-08 | Duquesne University Of The Holy Ghost | Directly compressible granules having improved flow properties |
IL96311A (en) | 1989-12-01 | 1995-05-26 | Abbott Lab | Medications with delayed release |
JPH04217925A (ja) * | 1990-03-27 | 1992-08-07 | Nippon Saafuakutanto Kogyo Kk | 新規な解熱消炎鎮痛剤組成物 |
DK0452145T3 (da) | 1990-04-12 | 1996-12-02 | Shionogi & Co | Overtrukket præparat og fremstilling deraf |
HU208495B (en) | 1990-06-27 | 1993-11-29 | Alkaloida Vegyeszeti Gyar | Process for producing retarde pharmaceutical compositions |
WO1992001446A1 (en) * | 1990-07-20 | 1992-02-06 | Aps Research Limited | Sustained-release formulations |
FR2665357B1 (fr) * | 1990-07-31 | 1995-03-31 | Aiache Jean Marc | Procede de preparation d'une forme galenique bio-adhesive et forme galenique ainsi preparee. |
GB2246514B (en) | 1990-08-01 | 1993-12-15 | Scras | Sustained release pharmaceutical compositions and the preparation of particles for use therein |
ES2075403T3 (es) | 1990-08-24 | 1995-10-01 | Spirig Ag Pharmazeutische Prap | Procedimiento para la fabricacion de pellets. |
JP2875611B2 (ja) * | 1990-08-29 | 1999-03-31 | エーザイ株式会社 | ケイ酸カルシウム含有外用剤 |
DE4031881C2 (de) * | 1990-10-08 | 1994-02-24 | Sanol Arznei Schwarz Gmbh | Lösungsmittelfreie, oral zu verabreichende pharmazeutische Zubereitung mit verzögerter Wirkstoffreisetzung und Verfahren zu deren Herstellung |
SE9003296L (sv) * | 1990-10-16 | 1992-04-17 | Kabi Pharmacia Ab | Foerfarande foer att formulera laekemedel |
US5271934A (en) * | 1990-10-22 | 1993-12-21 | Revlon Consumer Products Corporation | Encapsulated antiperspirant salts and deodorant/antiperspirants |
CA2041774C (en) | 1990-11-27 | 1994-04-19 | Mircea A. Mateescu | Use of cross-linked amylose as a matrix for the slow release of biologically active compounds |
US5603956A (en) | 1990-11-27 | 1997-02-18 | Labopharm Inc. | Cross-linked enzymatically controlled drug release |
US5403593A (en) | 1991-03-04 | 1995-04-04 | Sandoz Ltd. | Melt granulated compositions for preparing sustained release dosage forms |
US5132142A (en) | 1991-03-19 | 1992-07-21 | Glatt Gmbh | Apparatus and method for producing pellets by layering power onto particles |
IT1245891B (it) * | 1991-04-12 | 1994-10-25 | Alfa Wassermann Spa | Formulazioni farmaceutiche a rilascio controllato per uso orale gastroresistenti contenenti acidi biliari e loro sali. |
IT1251153B (it) | 1991-08-06 | 1995-05-04 | Vectorpharma Int | Composizioni farmaceutiche solide per somministrazione orale aventi proungata residenza gastrica |
MY110317A (en) | 1991-09-06 | 1998-04-30 | Mcneilab Inc | Compositions comprising a tramadol material and any of codeine, oxycodone or hydrocodone, and their use. |
US5215758A (en) | 1991-09-11 | 1993-06-01 | Euroceltique, S.A. | Controlled release matrix suppository for pharmaceuticals |
GB9121204D0 (en) | 1991-10-04 | 1991-11-20 | Euro Celtique Sa | Medicament |
WO1993007859A1 (en) * | 1991-10-23 | 1993-04-29 | Warner-Lambert Company | Novel pharmaceutical pellets and process for their production |
AU661723B2 (en) | 1991-10-30 | 1995-08-03 | Mcneilab, Inc. | Composition comprising a tramadol material and a non-steroidal anti-inflammatory drug |
US5162117A (en) * | 1991-11-22 | 1992-11-10 | Schering Corporation | Controlled release flutamide composition |
US5266331A (en) | 1991-11-27 | 1993-11-30 | Euroceltique, S.A. | Controlled release oxycodone compositions |
US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
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 |
US5286493A (en) | 1992-01-27 | 1994-02-15 | Euroceltique, S.A. | Stabilized controlled release formulations having acrylic polymer coating |
US5472712A (en) | 1991-12-24 | 1995-12-05 | Euroceltique, S.A. | Controlled-release formulations coated with aqueous dispersions of ethylcellulose |
US5958459A (en) | 1991-12-24 | 1999-09-28 | Purdue Pharma L.P. | Opioid formulations having extended controlled released |
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 |
GB2287880A (en) | 1994-03-14 | 1995-10-04 | Euro Celtique Sa | Production of sustained release compositions |
US5167964A (en) | 1992-02-14 | 1992-12-01 | Warner-Lambert Company | Semi-enteric drug delivery systems and methods for preparing same |
SE9200858L (sv) * | 1992-03-20 | 1993-09-21 | Kabi Pharmacia Ab | Metod för framställning av pellets med fördröjd frisättning |
JP2568202Y2 (ja) | 1992-10-13 | 1998-04-08 | オリエンタル写真工業株式会社 | ロール状材料用マガジン |
DE4236752A1 (de) | 1992-10-30 | 1994-05-05 | Asta Medica Ag | Kombinationspräparat aus Flupirtin und Morphin zur Behandlung von Schmerzen und zur Vermeidung der Morphin-Abhängigkeit |
US5321012A (en) | 1993-01-28 | 1994-06-14 | Virginia Commonwealth University Medical College | Inhibiting the development of tolerance to and/or dependence on a narcotic addictive substance |
US5616343A (en) | 1993-03-25 | 1997-04-01 | Labopharm, Inc. | Cross-linked amylose as a binder/disintegrant in tablets |
SE9301057L (sv) * | 1993-03-30 | 1994-10-01 | Pharmacia Ab | Beredning med kontrollerad frisättning |
NZ260408A (en) | 1993-05-10 | 1996-05-28 | Euro Celtique Sa | Controlled release preparation comprising tramadol |
IL110014A (en) | 1993-07-01 | 1999-11-30 | Euro Celtique Sa | Solid controlled-release oral dosage forms of opioid analgesics |
IL109944A (en) | 1993-07-01 | 1998-12-06 | Euro Celtique Sa | Continuous release dosage form containing morphine and a method of preparing such sustained release unit dosage forms |
DE4329794C2 (de) * | 1993-09-03 | 1997-09-18 | Gruenenthal Gmbh | Tramadolsalz enthaltende Arzneimittel mit verzögerter Wirkstofffreisetzung |
US5891471A (en) | 1993-11-23 | 1999-04-06 | Euro-Celtique, S.A. | Pharmaceutical multiparticulates |
KR100354702B1 (ko) | 1993-11-23 | 2002-12-28 | 유로-셀티크 소시에떼 아노뉨 | 약학조성물의제조방법및서방형조성물 |
US5395626A (en) * | 1994-03-23 | 1995-03-07 | Ortho Pharmaceutical Corporation | Multilayered controlled release pharmaceutical dosage form |
GB9422154D0 (en) | 1994-11-03 | 1994-12-21 | Euro Celtique Sa | Pharmaceutical compositions and method of producing the same |
US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
GB9519363D0 (en) | 1995-09-22 | 1995-11-22 | Euro Celtique Sa | Pharmaceutical formulation |
CA2173818A1 (fr) | 1996-04-10 | 1997-10-11 | Francois Chouinard | Comprime pharmaceutique a liberation controlee contenant un support a base d'amylose reticule et d'hydroxypropylmethylcellulose |
WO1999001111A1 (en) | 1997-07-02 | 1999-01-14 | Euro-Celtique, S.A. | Stabilized sustained release tramadol formulations |
TR200001828T2 (tr) | 1997-12-22 | 2000-11-21 | Euro-Celtique, S.A. | Opioid dozaj şekillerinin kötüye kullanımını önlemeye yönelik bir yöntem. |
US6284273B1 (en) | 1998-02-24 | 2001-09-04 | Vincent Lenaerts | Cross-linked high amylose starch resistant to amylase as a matrix for the slow release of biologically active compounds |
US6607748B1 (en) | 2000-06-29 | 2003-08-19 | Vincent Lenaerts | Cross-linked high amylose starch for use in controlled-release pharmaceutical formulations and processes for its manufacture |
US6338859B1 (en) | 2000-06-29 | 2002-01-15 | Labopharm Inc. | Polymeric micelle compositions |
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1994
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US7968120B2 (en) | 2001-09-28 | 2011-06-28 | Mcneil-Ppc, Inc. | Modified release dosage forms |
US7972624B2 (en) | 2001-09-28 | 2011-07-05 | Shun-Por Li | Method of manufacturing modified release dosage forms |
US8545887B2 (en) | 2001-09-28 | 2013-10-01 | Mcneil-Ppc, Inc. | Modified release dosage forms |
CN100411611C (zh) * | 2002-04-05 | 2008-08-20 | 欧洲凯尔蒂克公司 | 用于持续,不变且独立释放活性化合物的基质 |
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 |
US8673352B2 (en) | 2005-04-15 | 2014-03-18 | Mcneil-Ppc, Inc. | Modified release dosage form |
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