CN1055617C - 口服药物剂型 - Google Patents
口服药物剂型 Download PDFInfo
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- CN1055617C CN1055617C CN93119318A CN93119318A CN1055617C CN 1055617 C CN1055617 C CN 1055617C CN 93119318 A CN93119318 A CN 93119318A CN 93119318 A CN93119318 A CN 93119318A CN 1055617 C CN1055617 C CN 1055617C
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- Prior art keywords
- encapsulating material
- acid
- film
- cellulose
- reactive compound
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Abstract
本发明涉及口服药物剂型，其包括至少一种活性化合物，至少一种包裹活性化合物的包封材料和至少一种不溶于水和消化液的成膜剂，其特征在于包封材料另外还包括至少一种环糊精或至少一种环糊精的衍生物。
Description
本发明涉及一种新的口服药物剂型，其包括至少一种活性化合物，至少一种包容此活性化合物的包封材料，至少一种不溶于水和消化液的成膜剂，其特征在于包封材料至少包括一种环糊精和/或至少一种环糊精的衍生物。
进一步说，本发明涉及一种口服药物剂型的包封材料，其包括至少一种不溶于水和消化液的成膜剂，其特征在于成膜剂还包括至少一种环糊精或至少一种环糊精的衍生物。
本发明目的在于提供口服药物剂型，其中的活性化合物在结肠内以控制的方式释放。这样的药物剂型本身是公知的。
通常，这些药剂包括一层在胃和小肠耐受的膜，它们在结肠内首先破裂因而使活性化合物释放出来。EP 0 485 840A2描述了一种膜剂，其包括能在结肠内破裂的多糖及与多糖混在一起的成膜聚合物材料。然而，这种膜剂仍然有一些缺点。比如，它们坚硬，活性化合物在结肠内并不总是特异性地释放。
DE 41 31 292 A1描述了用于包埋活性药物的乳甘露聚醇衍生物，这些乳甘露聚醇衍生物是新物质，它们的毒理耐受性至今还没有被阐明。
另外，例如就微胶囊和半透包袋来说，比如乙基纤维素，药物释放的个体差别很大。
上述口服药物剂型可以避免或至少可以减少这些已知药物剂型的缺点。
详细地说，适当的药物剂型是片剂，包衣片剂、Sachets、胶囊、丸剂、喷射剂、粒剂、晶体或散剂。这些药物剂型也可包入包封材料内，包封材料内至少包括一种活性化合物，至少一种存在于不溶于消化液的成膜剂中的环糊精。
按照本发明，较合适的成膜剂是聚丙烯酸酯、聚甲基丙烯酸酯或它们的共聚物、乙基纤维素，尤其是高度取代的乙基纤维素。商业用分散剂包括丙烯酸酯和甲基丙烯酸酯的共聚物，并含有少量的季铵基团，这些铵基与其它中性(甲基)丙烯酸酯的摩尔比在大约1∶10和1∶50之间，最好在1∶20和1∶40之间，且平均分子量约为150,000，这样的分散剂应用起来特别有益。
本发明采用的环糊精是α-配糖连接的寡糖，而依照EP 0 485840 A2采用的是β-配糖连接的多糖。
优选的环糊精是β-环糊精(“CD”；七个葡萄糖残基)。而α-环糊精(六个葡萄糖残基)和γ-环糊精(八个葡萄糖残基)也是适用的。环糊精衍生物可是羟丙基-CD，羟乙基-CD和聚-CD。
依照本发明，包封材料可进一步包括辅助材料或添加剂。加入增塑剂是有益的，特别适合的增塑剂是二羧酸烷基酯或三羧酸烷基酯，例如邻苯二甲酸二乙酯(“DEP)或柠檬酸三乙酯(“TEC”)。在极化显微镜下看到：CD以基本不变的形式出现在含TEC的材料中，而就含DEP材料来说，可以看到结晶结构。其它适当的增塑剂是，例如，(其它)柠檬酸酯和酒石酸酯(乙酰三乙基，乙酰三丁基和三丁基柠檬酸酯)；甘油和甘油酯(二乙酸甘油酯，三乙酸甘油酯，乙酸单甘油酯和蓖麻油)；邻苯二甲酸酯(二丁基，二戊基，二甲基，二丙基和二2-甲氧基或二乙氧基乙基邻苯二甲酸酯，乙基邻苯二甲酰基、丁基邻苯二甲酸乙基和丁基乙二醇酯)；醇(丙二醇，不同链长的聚乙二醇)；己二酸酯(二乙基、二2-甲氧基或二乙氧基乙基乙二酸酯)；二苯甲酮；二乙基和二丁基的癸二酸酯、丁二酸酯、和酒石酸酯；二丙酸乙二醇酯；二乙醇的二乙酸酯、二丁酸酯和二丙酸酯；三丁基磷酸酯和三丁酸甘油酯；聚乙二醇脱水山梨醇单油酸酯；脱水山梨醇单油酸酯；聚氧乙烯醚与聚氧丙烯醚的嵌段聚合物。
加入少量水溶性物质，例如聚乙醇，聚乙烯吡咯烷酮，醋酸聚乙烯酯，羟丙基纤维素和羟丙基甲基纤维素等，是可能的。像滑石和硬脂酸镁这样的固体及颜料、色素也可被加到包封材料中。而且，加入像20-30％的硬脂酸这样的亲脂性物质可抑制膜对水蒸汽的渗透性，因而可提高对潮湿敏感物质的贮存期。
如果适当，可以在核心材料与辅助材料之间应用一个绝缘层，例如绝缘层可以包括羟丙基纤维素，羟丙基乙基纤维素或聚乙烯吡咯烷酮。
最后也可以应用保护漆。例如，适于的保护漆的物质可以是乙酰邻苯二甲酸纤维素酯，邻苯二甲酸羟丙基乙基纤维素酯，聚乙烯邻苯二甲酸乙酰酯、紫胶、乙酰丁二酸羟丙基乙基纤维素酯、羧甲基纤维素、乙酰三苯六甲酸醋纤维素酯，马来酸衍生物与邻苯二甲酸衍生物的共聚物。
有利的包封材料包括30-90％最好40-75％的成膜剂，0-30％最好8-15％的增塑剂，10-70％最好12-50％的环糊精。
包封活性化合物或活性化合物与常规的或必要的药物辅料包容在一起的药物组合物，由公知的药物生产技术方法或通常的包衣药物剂型的方法来制备。
有治疗活性的化合物同样按公知的药物生产技术包封。本发明的包封材料用于替代惯用至今的塑性物和可熔包封材料，例如石蜡，氢化蓖麻油，纤维素醚或酯，聚(甲基)丙烯酸酯。而且习惯应用的药物辅助料或添加剂这里也可以被混合应用，例如，增塑剂，香料，甜味剂，辅料如滑石、碳酸钙、甘露糖醇、纤维素粉，可溶颜料和色素。
辅料按所用环糊精重的10-100％，最好20-40％的重量比加到包封材料中。
香料、甜味剂和颜料可以少量，比如0.001％到2％，加入混合物中。
关于常用辅料及添加剂的进一步资料可在技术文献中找到，例如J.H.Saunders和K.C.Frisch写的专著“High Polymers”，Verlag Interscience Publishers，1962和1964。
喷射有机溶剂中的溶液或前面提到有机溶剂或水中物质的悬浮液或分散液对包封是有利的，加入另外的辅料例如表面活性剂或色素，也是允许的。
可以用涂层水壶或穿孔水壶或空气悬浮液或流化床方法(例如Glatt fluidized bed Unit USG5)进行喷射。
也可以用凝聚法进行包封，从而形成所谓的微胶囊或微粒。
也可以用分散相或悬浮相水溶液的凝结法来进行包封，其在上述物质的最小成膜温度以上，将活性化合物与分散液混合，然后干燥去水。
被包衣的活性化合物颗粒或包衣颗粒可被压制成片剂，可以把包衣丸剂插入硬的凝胶胶囊内。
为了包封活性化合物颗粒，与采用片剂或丸剂形式相比，需要使用较多的包封材料，因为颗粒需要覆盖的表面比使用丸剂或片剂形式需要覆盖的表面显著增大。
由于片剂通常比丸剂大，所以片剂需要覆盖的表面相应较小。例如，每份重的活性化合物或药物组合物可用0.02-1份重的包封材料。1份重的活性化合物比0.04-0.7份；尤其0.05-0.7份，重的包封材料是优选的，比0.1-0.7份重的包封材料是特别优选的。在高温下，最好是空气流下(进料温度60-120℃；流出温度100℃)应用溶液，悬浮液、分散液中包封材料是方便的。
就包封方法而言，例如，每份重的活性化合物应用0.05-5.0份重的包封材料，优选0.08-3.0份重的包封材料，特别优选0.1-2.0份重的包封材料。在10℃-100℃之间可以方便地制备这些药物组合物。
制剂形式的制备可如下进行：
a)按照本发明，将活性化合物或其盐溶解或分散在包封材料或其混合物中，随着前述物质的熔融，随后再冷却，粉碎，也可能加入其它物质，例如水溶性的或水中膨胀的物质，然后压成片剂，熔化物冷却及粉碎也可结合成进一步完成，方法是将熔化物分散在冷水中或把它喷射固化。
可能的膨胀物质是，例如：甲基纤维素，羟乙基纤维素，羟丙基纤维，羟丙基乙基纤维素(纤维素丙氧基醚、乙氧基醚和甲氧基醚取代物)，藻酸及其盐(钠盐、钙盐、藻酸钠与钙盐，例如CaHPO4，的混合物)，淀粉，羧甲基淀粉，羧甲基纤维素及其盐(例如钠盐)，阿拉伯树胶，刺梧桐胶，茄替胶，琼脂，角叉菜，合成生物聚合胶，丙二醇藻酸酯，果胶和黄蓍糖。
b)按照本发明将活性化合物与包封材料混合，也可以加入适当的膨胀性物质或其混合物，也可使用加热，当加入其它辅料后适当时，把混合物压成片剂或制成丸剂和粒剂。
c)按照本发明将活性化合物与包封材料在诸如乙醇、乙酸乙酯、丙酮或异丙醇的有机溶剂中的溶液混合，如果适当可混入像纤维素这样的载体材料，随后蒸去溶剂，获得的包封活性化合物再与辅料混合，压成成形的颗粒，例如片子、粒子或丸子。
d)按照本发明将活性化合物与包封材料的混合物润湿，如果合适可加入上述膨胀性物质和乙醇、乙酸乙酯、丙酮或异丙醇等有有机溶剂，也可加入像聚乙烯吡咯烷酮或聚乙烯咯烷酮和聚乙烯乙酸酯的共聚物这样的结合剂，把所得混合物粒化，随后干燥，加入其它辅料，将混合物压成片剂。
制备这些药物剂型方法本身是相当普遍的公知方法，按照本发明，公知的和常用的药物辅料及其它常用的赋形剂和稀释剂都可被加到包封材料中。
可用的赋形剂和稀释剂可以是被建议用在药剂，化妆品和下列参考文献的相关领域作为辅料的物质：Ullmanns Encyklopdie der technischen Chemie(UllmannsEncyclopaedia of Industrial Chemistry)，Volume 4(1953)，pages 1 to 39；Journal of Pharmaceutical Sciences，Volume52(1963)，page 918 et seq.，H.V.Czetsch-Lindenwald，Hilfsstoffe für Pharmazie und angrenzende Gebiete(Auxiliaries for Pharmacy and Related Fields)；Pharm.Ind.，Volume 2，1961，page 82 et seq.；andDr.H.P.Fiedler，Lexikon der Hilfsstoffe für Pharmazie，Kosmetik und angrenzende Gebiete (Dictionary ofAuxiliaries for Pharmacy，Cosmetics and Related Fields)，2nd Edition，Editio’Cantor，Aulendorf in Württemberg(1981).
常用辅料、赋形剂、稀释剂的例子是明胶、天然糖，如蔗糖或乳糖、卵磷脂、果胶、淀粉(如玉米淀粉)和淀粉的衍生物，乳甘露聚糖，聚乙烯吡咯烷酮，凝胶，阿拉伯树胶，藻酸，纤基乙酸钠，滑石，硅酸(如胶体)或高分散SiO2，果糖，黄蓍胶，氯化钠，硬脂酸盐，含12-22个碳原子的脂肪酸尤其是饱和脂肪酸(如硬脂肪酸盐)的镁盐和钙盐，平均分子量为200-20,000，最好200-5000，尤其200-1000的聚乙二醇或其混合物，聚乙烯吡咯烷酮，乙烯吡咯烷酮和乙酸乙烯酯的共聚物，脂肪族饱和或不饱和脂肪硬脂(2-22个碳原子，尤其10-18个碳原子)和单羟脂肪醇(1-20个碳原子)或多羟醇，如乙二醇、丙二醇、二甘醇。季戊四醇、山梨醇、甘露糖醇和其它能被选择性酯化的类似物，苯甲酸苯甲酯，二氧戊环，丙三醇缩甲醛，四氢糠醇，聚乙二醇与含1-12个碳原子醇形成的醚，二甲基乳酰胺，乳酰胺，乳酸酯，碳酸乙基酯，聚硅氧烷(尤其是中性粘度的聚二甲基硅氧烷)，碳酸钙，碳酸钠，磷酸钙，磷酸钠，碳酸镁，阿拉伯树胶，藻酸，硬脂酸酯，脂肪和有类似作用的物质。
另外，此药剂型可包含表面活性剂。可以提到的例子是：碱金属皂，如高级脂肪酸的碱金属盐(例如棕榈酸钠或硬脂酸钠)或其衍生物(例如蓖麻醇酸钠硫酸酯)；高级脂肪醇与硫酸或氯磺酸反应生成的硫化物或磺化物如钠盐(例如十二烷基硫酸钠；十六烷基硫酸钠，十八烷酰硫酸钠，十六烷基磺酸钠)；胆酸盐；皂草苷；季铵化合物；疏水山梨醇的部分脂肪酸酯；聚氧乙烯疏水山梨醇的脂肪酸酯和部分脂肪酸酯，聚氧乙烯的山梨醇醚；聚氧乙烯的脂肪酸酯；脂肪醇聚氧乙烯醚；蔗糖脂肪酸酯；脂肪酸聚甘油酯；蛋白质和卵磷酯。
此药物剂型也包含填料，尤其是压片制剂时。可用填料是：纯化的纤维素或微晶纤维素，磷酸氢钙，乳糖，淀粉(如土豆淀粉，玉米淀粉)，葡萄糖，甘露糖醇，蔗糖，具有结合功能的填料，如微晶纤维素，水解的或部分断裂的淀粉及纤维素粉与乳糖的混合结晶。
本药物剂型也可以包括流动调节剂，例如：高度分散的硅酸。而且本药物剂型也可应用模释放剂。可提到的模释放剂是：滑石或硅氧烷化滑石，硬脂酸钙，硬脂酸镁，硬脂酸，石蜡，氢化脂肪，油，硅氧烷油乳液。然而，通常未必要加模释放剂，由于环糊精本身也有模释放剂特征。
其它可用的辅料也可以是引起崩解的物质(崩解剂)，如交联的聚乙烯吡咯烷酮，羧甲基钠淀粉，羧甲基纤维素钠，甲醛交联的明胶，甲醛交联的酪蛋白，聚丙烯酸和超支链淀粉。
加入稳定剂，颜料，抗氧剂，络合剂(如乙二胺四乙酸)，酸，如柠檬酸、酒石酸、马来酸、富马酸也是可以的。
可以应用的抗氧剂是：偏二亚硫酸钠，半胱氨酸、抗坏血酸及其酯(如其棕榈酸酯)，黄酮类似物(flavanoids)，没食子酸烷基酯，丁基羟基苯甲醚，nordihydroguajetic acid，生育酚，生育酚+增效剂(通过络合作用键合上重金属物质，如卵磷脂，抗坏血酸，柠檬酸和磷酸)。
可用作防腐剂的例子有：山梨酸、对羟基苯甲酸酯(如其低级烷基酯)，苯甲酸，苯甲酸钠，三氯异丁基醇，苯酚，甲苯酚，氯化苄乙氧铵和福尔马林衍生物。
按照本发明可用作包封材料的溶剂包括：水溶剂，醇，酮，醚，脂肪烃，卤代烃，环烃，杂环溶剂)及其混合物，除别的以外，典型的溶剂中：丙酮，双丙酮醇，甲醇，乙醇，异丙醇，丁醇，乙酸甲酸，乙酸乙酯，乙酸异丙酯，乙酸正丁酯，甲基异丁基酮，甲基丙基酮，正己烷，正庚烷，乙基乙二醇单乙基醚，乙酸乙二醇单乙酯，二氯甲烷，1，2-二氯乙烷，1，2-或1，3-二氯丙烷，四氯化碳，硝基乙烷，硝基丙烷，四氯乙烷，环己烷，环辛烷，苯，甲苯，石脑油，1，4-二噁烷，四氢呋喃，二乙二醇二甲基醚，水及其混合物，如丙酮和水，丙酮和甲醇，丙酮和乙醇，二氯甲烷和甲醇，1，2-二氯乙烷和甲醇。在包封过程中再除去这些溶剂。
按照本发明，能与包封材料结合的可能活性化合物是那些能口服给药的化合物，且期望它们仅在结肠释放。这些药物包括肠胃药，如mesalazine(5-氨基水杨酸)或轻泻药，如双醋甲啶，肽，心血管治疗药，抗风湿药/止痛药，治疗大肠疾病药(节段性回肠炎，溃疡性结肠炎)，抗哮喘药，抗血纤维蛋白溶解药，抗出血药，抗癌药，酶制剂，抗生素，抗真菌药和作用在中枢神经系统的药物。
一类仅在结肠释放的重要化合物是那些具有肽或蛋白结构的药物，例如胰岛素。在它们产生作用之前位于肠上部的内源蛋白水解酶将使它们破裂。相对而言，结肠内蛋白水解酶含量很低，以致于需要保持足够的作用和吸收时间。
特别指出的肽类活性化合物的例子是：ACTH(促肾上腺皮质激素)，Corticostatin，降钙素，胰岛素，催产素，生长激素(Somatostatin)及类似物，LHRH类似物，bombesin类似物，缩胆囊素及其衍生物，内皮素及其类似物，凝血酶抑制剂，肽生长因子(如：IGF，EGF，MGF)，magainins(PGS肽)，胃酶(gastric)类似物，甲状旁腺类似物，神经激肽及类似物，VIP(作用血管的肠多肽)及类似物，ANP(前房排钠利尿肽)及类似物，新京都啡呔及类似物，血管紧张肽类似物，脑磷脂，dynorphins，dermophins，deltorphins，抑制血管紧张肽原酶的肽，癌生长因子肽，MSH(黑素细胞剌激激素)类似物，线毒素(mitotoxins)，tyrphostins，chromogranin A，thymopentin，TRH(促甲状腺激素释放激素)及类似物，P物质，tuftsin，fibronectin及肽的免疫复制物，如环孢多肽A，FK 506和神经肽Y。
本发明的包封材料对模拟的小肠肠液实际上是不能通透的。在“结肠微菌丛测试”(“CMT”；对比C.Wohlschlegel，Freiburg1990年有学术论文)培育后，另一方面，产生酶解CD作用，由此膜变成有孔的，因而可通透，这样被包封的活性化合物可被释放出来并在结肠内起作用。
新型包封材料的一个特殊优点在于它的组分是公知的并且是生理上可完全耐受的。
上文及下文的所有百分比数据是重量区分比，温度是摄氏温度。
实施例1：包封材料(膜)1.1制备
把4gDEP和4gCD在27.3ml水中的分散液混合，在2分钟内将此混合物加到66.6g 30％共聚物水相分散液(商用制剂)中，此共聚物组成为30％的丙烯酸乙酯、65％的甲基丙烯酸甲酯和5％的氯化甲基丙烯酸三甲基胺乙基酯，同时搅拌(每分钟180转)，此混合物在此温度下继续搅拌10分钟。
为了表示膜的特征，于40℃下用509/1型Erichsen拉膜仪在聚酯膜上从分散液中将膜拉出，拉速为12毫米/秒。用刀口高度为200μm的刮刀进行拉膜，成膜时间约需30分钟，然后刮膜保持在20-25℃的聚酯膜上，再与载体膜分开用于实际表征。
下面组合的分散液同样可获得(按％)No. 增塑剂 CD 水
成膜剂 TEC DEP1 19.23 3.85 0 3.85 73.072 19.23 3.85 0 5.77 71.153 19.23 3.85 0 7.69 69.234 19.23 0 3.85 3.85 73.075 19.23 0 3.85 5.77 71.156 19.23 0 3.85 7.69 69.237 19.23 0 3.85 9.62 67.308 17.24 0 3.45 10.34 68.979 16.95 0 3.39 11.86 67.8010 16.66 0 3.33 13.33 66.6811 16.39 0 3.28 14.75 65.5812 16.13 0 3.23 16.13 64.5113 15.63 0 3.13 18.75 62.49
1.2膜特征
1.2.1膜厚度测定
膜厚度由磁感应方法(Minitest 3000，Erichsen)测定。在6个不同点进行测定，得到测定的平均结果。膜厚度在35-75μm之间。
1.2.2.在模拟小肠液内的渗透性
借助于Franz细胞(对比C.L.Gummer et al.，Int.J.Pharm.40(1987))101-104)就膜的通透性进行了研究。对此，将一片膜夹在供体和受体之间。受体容器内充满模拟小肠液(磷酸缓冲溶液pH6.8R DAB10)并保持控制在37℃。用磁力搅拌器将液体彻底混合。供体含有一浓的mesalazine溶液(5μg/ml)，pH为6.8的磷酸缓冲溶液为溶剂。药物用作膜通透性的指示物质。2小时、4小时、6小时后，从受体中取出2ml样品，同时补充2ml磷酸缓冲溶液。用光度法测量样品(Uvikon 820，Wavelength 330nm)，检测限为2μg/ml。借助于在受体中测定mesalazine浓度来测定膜的通透性。在这些实验条件下近6小时内上面1.1部分提到的所有膜几乎都是不通透的。
1.2.3在CMT(结肠微菌丛试验)中的降解性
CMT(对比Pharm.pharmacol.Lett(1992)，2，62-65)习惯上用于检查在大肠内的降解性。这是猪肓肠、回肠造口术病人的排泄分泌物和pH为6.4R，DAB10(5∶5∶1)的磷酸冲溶液的混合物，该混合物在厌氧条件下培育，也就是说在37℃以5∶1的比例通入N2/CO2的条件下。
把半径约为0.7cm的圆膜片用回肠造口术/猪肓肠混合物培育一定的时间(2至6小时之间)，然后用水冲洗并在室温下干燥。为了制备样品，把膜片贴到显微镜载波片上喷金。用扫描电子显微镜检查膜的表面，与没有用CMT处理的样品对比，发现此膜样品表面具有大孔结构。
实施例2：包封材料(膜)
将1.2g DEP和4.75g CD在36.3g水中的分散液的混合物在2分钟内加到50g 25％的乙基纤维素的水分散液中(商业用)，同时搅拌(每分钟180转)，此混合物在室温下继续搅拌15分钟。
同样，下列组成的分散液可以获得(以％计)No. 增塑剂 CD 水
成膜剂 TEC DEP DBS*)1 11.93 1.45 0 0 3.44 83.182 10.70 1.30 0 0 5.15 82.853 11.93 0 1.45 0 3.44 83.184. 10.70 0 1.30 0 5.15 82.855 11.93 0 0 1.45 3.44 83.186 10.70 0 0 1.30 5.15 82.85DBS＝癸二酸二丁基酯实施例3：包衣片剂3.1制备
把330g实施例1.1中商业用分散液与20g TEC和30g CD在370ml水中悬浮液用旋桨搅拌器搅拌使之混合，然后混合物继续搅拌10分钟。
1.5kg下列组成的片芯用这种分散液喷洒：Mesalazine 100mg微晶纤维素 35mg乳糖 35mg聚乙烯吡咯烷酮 7mg玉米淀粉 20mg高分散硅酸 3.6mg羧甲基纤维素钠盐 1.8mg硬脂酸镁 1.8mg
204.2mg
(直径8mm；高3.76mm；表面积1.96cm2)
喷洒过程中用旋浆搅拌器搅拌分散液(持续的喷洒过程，喷入3巴的空气；流速为10g/分钟；喷嘴直径0.6mm；温度：入口63℃，中心33℃，出口44℃；喷射时间约为1小时)。结果每个片子包衣17.6mg包封材料，然后在40℃下干燥过夜。3.2片剂的特征3.2.1在人工结肠内的稳定性
为了测试片剂在人工结肠内的稳定性，把片剂移到降解试验容器内保持6小时，随后进行光学测定。测定受试介质内mesalazine的浓度。在这些条件下，全部片剂至少稳定6小时。3.2.2在CMT中的降解性
把片剂放在CMT中培育4、6和24小时，随后在搅拌器内测定它们的释放特征。结果发现随着CD含量增高和培育时间增长，片剂的通透性增加。
实施例4：包衣片剂
根据实施例2,500g乙基纤维素的商业用分散剂通过用旋浆搅拌器搅拌与12g TEC和47.5g CD在670.5ml水中的悬浮液进行混合。混合物继续搅拌10分钟，然后按照实施例3中操作步骤进行操作。
Claims (4)
1.一种口服药物剂型，其含有至少一种活性化合物和至少一种包封材料，所述包封材料包裹着活性化合物并含有至少一种不溶于水和消化液的成膜剂，其特征在于包封材料另外还含有至少一种来自α-配糖连接的寡糖的环糊精和/或至少一种其衍生物，以及增塑剂。
2.根据权利要求1的口服药物剂型，其中所述增塑剂为邻苯二甲酸二乙酯、柠檬酸三乙酯或癸二酸二丁酯。
3.一种口服药物剂型的包封材料，其含有至少一种不溶于水和消化剂的成膜液，其特征在于包封材料另外还含有至少一种来自α-配糖连接的寡糖的环糊精和/或至少一种其衍生物，以及增塑剂。
4.根据权利要求3的口服药物剂型的包封材料，其特征在于所述增塑剂为邻苯二甲酸二乙酯、柠檬酸三乙酯或癸二酸二丁酯。
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| EP0595110A1 (de) | 1994-05-04 |
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