CN1150893C - 带两层包衣的药物组合物 - Google Patents

带两层包衣的药物组合物 Download PDF

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CN1150893C
CN1150893C CNB988076217A CN98807621A CN1150893C CN 1150893 C CN1150893 C CN 1150893C CN B988076217 A CNB988076217 A CN B988076217A CN 98807621 A CN98807621 A CN 98807621A CN 1150893 C CN1150893 C CN 1150893C
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chewable tablets
oil
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CN1265029A (zh
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G��A���ֶ���
G·A·沃尔特
R·W·申
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Fa Masi Jaap strong Company Limited
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    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings

Abstract

本发明提供一种药物组合物，它基本上没有令人不快的口味并可口服，它包括：(a)活性药物，(b)内包衣层，含熔点为约50℃～100℃的油性物质，和(c)外包衣层，含至少一种聚合物。

Description

带两层包衣的药物组合物
本发明涉及口服药物组合物。更具体地说，本发明涉及带两层包衣的含有活性成分的药物组合物，该组合物基本上没有不良口味。
茶苯海明是一种预防和治疗晕动病的已知药物。但象许多药物，尤其是带胺或酰氨基的药物一样，它带有强烈的苦味。如果不适当掩盖味道，茶苯海明和这类药物就不适于成为口服形式，尤其是咀嚼片形式。目前的味道掩盖技术，包括将药物用简单的聚合物包衣，对茶苯海明的味道掩盖不能达到完全令人满意的程度，这是由于它在水性介质和各种有机溶剂中具有显著的溶解度。因此常规包衣方法中使用的溶剂常常部分溶解该药物，使药物暴露于制剂的表面。
认识到这一问题，本发明旨在研究具溶解性的活性药物，如茶苯海明，即同时具有显著溶于有机溶剂和显著溶于水性介质的能力的药物的味道掩盖包衣制剂。我们发现通过使用两层适当包衣包覆活性药物可基本上掩盖不良口味。
日本专利116652的摘要公开使用石蜡、蜂蜡、高级醇和/或脂肪酸(酯)生产蜡包衣的颗粒药物产品。
国际公开WO 94/08576公开了一种基本上没有雷尼替丁苦味的组合物，它包括a)雷尼替丁或其生理可接受的盐的脂质包衣颗粒在非水性载体中的分散体，b)所述颗粒包含掺入核芯的雷尼替丁或其生理可接受的盐并用脂质包衣层包衣，和c)所述脂质包衣颗粒形式的雷尼替丁不溶于水。
欧洲专利申请0409254A1公开了快速释放的口服颗粒药物制剂，该制剂的令人不快的味道被掩盖，该制剂包括一个核芯和一个包衣该核芯的膜层，该核芯至少含一种具有不良口味的药物和一种水溶胀物质，膜层至少含乙基纤维素和一种水溶性物质。
本发明的目的是提供一种含活性药物的口服药物组合物，该组合物基本上不带有与活性药物有关的不良口味。
本发明的另一个目的是提供一种口服药物组合物，它含有即可显著溶于有机溶液又可显著溶于水性介质的活性药物。
本发明的另一个目的是提供一种口嚼片形式的含活性药物的药物组合物，它具有良好的口味、美好的外观和适当的硬度。
本发明的目的通过提供了一种基本上不带有不良口味并能口服的药物组合物得以完成，该组合物含：
(a)活性药物，
(b)含熔点为约50℃～100℃的油性物质的内包衣层，
(c)含至少一种聚合物的外包衣层。
依据本发明，提供了一种基本上不带苦味的药物组合物。
本发明由带内包衣层和外包衣层的活性药物形成。活性药物是可溶于有机溶液和水性介质的药物。然而，本发明的组合物虽对这类药物最具重要实用性，但也可适用于所有的药物活性物质。
本发明的适宜组合物包括带内包衣层的活性药物，形成内核芯，以组合物的内核芯重量计，其中的活性药物量为约5％～65％，内包衣层的量为约95％～35％。以组合物的内核芯重量计，优选的内核芯组合物含有约50％的核芯药物和约50％的内包衣层。组合物中活性药物的量可根据使用的特定活性药物和所需的浓度加以调整。
用于形成组合物内包衣层的油性物质包括各种可药用的、与水不相混溶的、熔点为约50℃～100℃的物质，例如氢化植物或动物油。例如，油性物质可以是氢化或部分氢化的大豆油、鳄梨油、角鲨烯油、芝麻油、橄榄油、低芥酸菜子油、玉米油、油菜籽油、红花油、向日葵油、鱼油、香油、水不溶性维生素或熔点至少为约50℃的聚乙二醇聚合物，以及它们的混合物。用于包衣层的优选的油是氢化大豆油。
本发明的药物组合物还包含一种聚合物作为外包衣层。用于外包衣层的适宜的可药用聚合物包括基于纤维素的聚合物，例如烷基纤维素，如甲基纤维素、乙基纤维素或丙基纤维素；羟烷基纤维素，例如羟丙基纤维素或羟丙甲基纤维素；和其它基于纤维素的聚合物，例如乙酸邻苯二甲酸纤维素、邻苯二甲酸羟丙甲基纤维素；和甲基丙烯酸共聚物；甲基丙烯酸氨基烷基酯共聚物；甲基丙烯酸酯共聚物；甘油三乙酸酯；柠檬酸三乙酯；乙酰基柠檬酸三乙酯；柠檬酸三丁酯；乙酰基柠檬酸三丁酯；邻苯二甲酸二乙酯；邻苯二甲酸二丁酯或癸二酸二丁酯。特别优选的聚合物是乙基纤维素，它可以是其任何可药用形式的，例如羟乙基含量为46.5％～51％和粘度为4～100厘泊(cps)的。除聚合物外，外包衣层可含有其它药物成分，例如适宜的增塑剂，如丙二醇、聚乙二醇400；或溶剂，如乙醇、异丙醇、丙酮或水。通常，聚合物的量占组合物总重的约4％～90％。内核芯的量占组合物总重的约90％～约4％，其它成分的量为约1％～约40％。在本发明的优选组合物中，聚合物的量为约20％～约40％，内核芯的量为约40％～约70％，其它成分的量为约1％～约5％。
如果需要，本发明的组合物还可含有常规的可药用辅剂，例如着色剂、调味剂、芳香剂、防腐剂、稳定剂、抗氧剂和/或增稠剂。
本发明的组合物可以呈口服的颗粒、片剂、弹丸剂、丸剂、粉末或胶囊形式。
本发明的一个重要特征是内包衣层中使用的油性物质应提供较大的柔韧性；因此，在压片过程中，本发明的组合物可被弯曲或折曲，而不会被损害，并且油包衣的小珠内的药物在咀嚼后不会被泄露出来。如此，可咀嚼片是本发明特别优选的药剂形式，它可通过压制适宜可咀嚼基质，如蔗糖、山梨醇、葡萄糖、木糖醇、甘露醇或它们的混合物的颗粒获得。
本发明的组合物可采用已知制备技术，例如采用热熔融包衣法形成内包衣层，然后将适宜的聚合物溶液喷雾到内核芯上来制备。下列制备例和实施例将以举例说明的方式更好地说明本发明，而非限制本发明的范围。无需进一步的精巧变化，据信本领域的普通专业技术人员将能够依据前面的描述和下列实施例中提供的信息，可使本发明得以最充分地实现。
制备例1用油包衣内层
茶苯海明                          5kg
Stearine Flake #17(氢化大豆油)    5kg
往一不锈钢容器中，加入Stearine Flakes并将其置于加热板上。使加热板加热熔化薄片并使批料温度保持在约80～85℃。在Glatt GPCC5上，隔离空气进气部件(包括喷嘴、喷嘴杆和雾化空气管线)。用空气加热器将喷雾空气预热到高于100℃。将茶苯海明加到Glatt产品容器中。当喷雾系统处于高温时，通过使用冷空气打开涡轮机。通过监视喷雾速率，将熔融的大豆油喷雾到茶苯海明上并使产品温度保持在约48℃以上直至将大豆油喷完。将产品冷却到约35℃，然后从Glatt产品容器中取出产品。使产品通过16目筛。
制备例2用聚合物包衣外层
Stearine包衣的茶苯海明                4kg
(50％活性成分)
乙基纤维素NF 4厘泊                    2kg
丙二醇USP(美国药典)                   220g
异丙醇                                14kg
丙酮                                  6kg
往适宜的容器中加入异丙醇、丙酮和丙二醇。缓慢搅拌的同时，将乙基纤维素加到上述溶剂中并混合直至所有的乙基纤维素溶解。往Glatt产物容器中加入Stearine包衣的茶苯海明。在下列操作参数条件下，将乙基纤维素溶液喷雾到该批料上：
产品温度：                            24～27℃
排气口温度：                          26℃
进气口温度：                          40℃
雾化空气：                            3巴
喷雾速率：                    135克/分
使二次包衣的产品通过16目筛。
制备例3咀嚼片(葡萄口味)
每1000片的配方：
二包衣的茶苯海明              152.0g
(32.9％活性成分)
甘露醇USP                     248.7g
山梨醇NF(国家处方集)          248.7g
苹果酸NF                      10.5g
天冬甜素NF                    7.0g
葡萄香料(喷雾干燥的，WL-261)  20.0g
FDC Red Lake#40               2.0g
FDC Blue Lake#1               10.6g
硬脂酸镁NF                    10.5g
将上述成分(不包括硬脂酸镁)加到Patterson-Kelley搅拌机中并搅拌30分钟。加入硬脂酸镁并搅拌3分钟。用压片机将物料压缩成片，片重为700mg/片，片的硬度为6～9 Strong Cobb单位。
片硬度：                      6～9 SCU
脆性：                        0.2％
口味：                        口味极佳，色泽美好
实施例1
A、
茶苯海明USP                   50％
氢化大豆油                    50％
B、
乙基纤维素NF 4厘泊    32.2％
油包衣的茶苯海明      64.3％
丙二醇                3.5％

Claims (10)

1、一种可咀嚼片剂，它含有可咀嚼基质以及如下所述的颗粒：每个颗粒含有
(a)活性药物，
(b)内包衣层，含熔点为50℃～100℃的油性物质，和
(c)外包衣层，它含至少一种聚合物，
其中的活性药物和内包衣层形成内核芯，
其中所述颗粒与可咀嚼基质压制混合，其中活性药物的量为内核芯总重的5％～65％，油性物质的量为内核芯总重的95％～35％聚合物的量为总颗粒量的4％-90％，并且当片剂被咀嚼时活性药物不会从内包衣层泄露出来。
2、权利要求1的可咀嚼片剂，其中的活性药物能溶于有机溶液和水性介质。
3、权利要求1的可咀嚼片剂，其中的活性药物是茶苯海明。
4、权利要求1的可咀嚼片剂，其中的油性物质是氢化或部分氢化的大豆油、鳄梨油、角鲨烯油、芝麻油、橄榄油、低芥酸菜子油、玉米油、油菜籽油、红花油、向日葵油、鱼油、香油、水不溶性维生素、聚乙二醇聚合物，以及它们的混合物。
5、权利要求1的可咀嚼片剂，其中活性药物的量为内核芯总重的50％。
6、权利要求1的可咀嚼片剂，其中油性物质的量为内核芯总重的50％。
7、权利要求1的可咀嚼片剂，其中的聚合物是甲基纤维素、乙基纤维素、丙基纤维素、羟丙基纤维素、羟丙甲基纤维素、乙酸邻苯二甲酸纤维素、邻苯二甲酸羟丙甲基纤维素、甲基丙烯酸共聚物、甲基丙烯酸氨基烷基酯共聚物、甲基丙烯酸酯共聚物、甘油三乙酸酯、柠檬酸三乙酯、乙酰基柠檬酸三乙酯、柠檬酸三丁酯、乙酰基柠檬酸三丁酯、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯或癸二酸二丁酯。
8、权利要求1的可咀嚼片剂，其中内核芯的量为可咀嚼片剂总重的90％～4％。
9、根据权利要求1的可咀嚼片剂，其中所述颗粒含有
(a)含量为20％～40％的含茶苯海明的活性药物，
(b)含量为20％～40％的含氢化或部分氢化的大豆油的内包衣层，和
(c)含乙基纤维素的外包衣层。
10、根据权利要求1的可咀嚼片剂，其中所述可咀嚼基质选自蔗糖、山梨醇、葡萄糖、木糖醇、甘露醇或它们的混合物。
CNB988076217A 1997-08-29 1998-08-25 带两层包衣的药物组合物 Expired - Fee Related CN1150893C (zh)

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