CN1965836A - 口服固体制剂及其制备方法 - Google Patents
口服固体制剂及其制备方法 Download PDFInfo
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- CN1965836A CN1965836A CNA200610146455XA CN200610146455A CN1965836A CN 1965836 A CN1965836 A CN 1965836A CN A200610146455X A CNA200610146455X A CN A200610146455XA CN 200610146455 A CN200610146455 A CN 200610146455A CN 1965836 A CN1965836 A CN 1965836A
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- Prior art keywords
- ibuprofen
- caffeine
- solid formulation
- oral solid
- preparation
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Abstract
本发明提供异丁苯丙酸的苦味及粘膜刺激性被掩蔽的口服固体制剂。异丁苯丙酸的苦味及粘膜刺激性被掩蔽的口服固体制剂的特征在于，将异丁苯丙酸、咖啡因、结晶纤维素和水溶性高分子湿式造粒后进行干燥而得。
Description
技术领域
本发明涉及异丁苯丙酸(布洛芬)的苦味及粘膜刺激明显地得到隐蔽的口服固体制剂。
背景技术
异丁苯丙酸是非甾体抗炎类药物之一，不仅作为治疗用药物被使用，在常用药领域中也被作为解热·镇痛·消炎药使用。
但是，异丁苯丙酸不仅显现出特别的令人不快的苦味，且服用后对喉部的粘膜刺激性非常强。因此，对于异丁苯丙酸，考虑对结晶粒子或造粒粒子包膜或添加大量的制剂添加物等掩蔽方法。
例如，专利文献1揭示了由异丁苯丙酸、乙基纤维素及增塑剂形成的治疗用无味喷雾干燥粉末，该粉末通过喷雾干燥溶解或悬浮有增塑剂的水中的异丁苯丙酸及乙基纤维素的分散液而形成。专利文献2揭示了对异丁苯丙酸、胃溶性高分子化合物、崩解剂及任意的医药领域所允许的赋形剂或载体等进行混炼造粒而获得的含异丁苯丙酸的口服用组合物。专利文献3揭示了令人不快的味道被掩蔽的造粒组合物，该组合物的特征在于，将带有令人不快的味道的成分在难溶于水的高分子物质的水分散液中造粒而形成造粒物，从该造粒物除去水分而获得。
此外，专利文献4记载了含异丁苯丙酸的颗粒剂及其制备方法，其特征在于，在用肠溶性高分子化合物对含异丁苯丙酸的混合物包衣而形成的包衣的含异丁苯丙酸的粒状物中加入赋形剂，再进行造粒，籍此能够提供苦味及刺激性得到抑制、易服用且经时稳定性良好的含异丁苯丙酸的颗粒剂。另外，专利文献5揭示了以较少的包覆量包覆药物表面而进行味道的掩蔽，经过一定时间后药物溶出而产生的味道得到了掩蔽的药物。即，药物的表面被包含以乙基纤维素为主成分的直径实质上在1μm以下的球形固体粒子、增塑剂和溶出控制剂的水性包覆液包覆而使味道得到掩蔽的药物，由于以较少的包覆量可确保药物的溶出，且(压缩)处理而导致的溶出变化较少，所以获得了极佳的味道得到了掩蔽的药物。
专利文献6揭示了以异丁苯丙酸、其异构体及其药学领域所允许的盐的粒状化微晶为基础的被覆粒子，该被覆粒子的特征在于，具备包含A)相对于异丁苯丙酸5～50重量％的乙基纤维素、B)相对于乙基纤维素10～60重量％的羟丙基甲基纤维素、C)相对于乙基纤维素0.1～40重量％的具备防静电及透过特性的二氧化硅的混合物所形成的被覆物质，前述被覆物质(至少其中的1种构成成分被用于制备前述粒子时的前述异丁苯丙酸的微晶的粒状化)掩蔽了异丁苯丙酸的令人不快的味道，明显地减弱了咽下后对喉部的刺激性作用，且前述粒子被置于水性介质中时，实质上可即时地释放异丁苯丙酸。
专利文献7揭示了味觉被掩蔽的药学组合物，该组合物通过用微晶纤维素组合物将药物湿润颗粒化，然后将该颗粒化物质颗粒球体化，使其形成为具有光滑的均一的表面及1～1000微米的范围内的粒子尺寸的球体而获得。
[专利文献1]日本专利第2688614号公报
[专利文献2]日本专利第2879905号公报
[专利文献3]日本专利特开2000-7557号公报
[专利文献4]日本专利特开平11-335279号公报
[专利文献5]日本专利特开2001-55344号公报
[专利文献6]日本专利特表2002-529399号公报
[专利文献7]日本专利特表2001-518491号公报
发明内容
但是，异丁苯丙酸的服用量通常成人1次大多数情况下作为治疗用药物为200mg，作为常用药为150mg，利用以往的掩蔽方法，在充分进行了掩蔽的同时，出现制剂的重量和体积都增大，药物制剂本身尺寸变大或1次的服用数量增多，服用变得困难的问题。此外，因为掩蔽方法的关系，还存在服用时不舒服或异丁苯丙酸的令人不快的味道的掩蔽虽然进行但粘膜刺激性作用依然残留，未能满足要求的问题。另外，大多数情况下制备时需要大量的有机溶剂，工序繁杂，制造成本增加，重现性也有问题。
因此，希望找到利用简单的方法，使重现性良好，制剂的重量增加较少，不使用大量的有机溶剂，易制备的异丁苯丙酸的苦味及粘膜刺激性作用的掩蔽方法。
本发明者为了达到上述目的进行探讨后发现，如果同时服用异丁苯丙酸和咖啡因，则异丁苯丙酸的苦味和粘膜刺激性会减弱。进一步进行认真研究后发现，将异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子湿式造粒后，经过干燥这样的简单工序而获得的口服固体制剂无需使用大量的制剂添加物及大量的有机溶剂等，虽然因为咖啡因的关系略有苦味，但异丁苯丙酸的苦味和粘膜刺激性作用同时有效地得到了完全地掩蔽，从而完成了本发明。
即，本发明提供了将异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子湿式造粒后进行干燥而获得的口服固体制剂。
此外，本发明提供口服固体制剂的制备方法，该方法的特征在于，将异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子湿式造粒后进行干燥。
本发明的口服固体制剂可通过简单的工序制备，异丁苯丙酸的苦味和粘膜刺激性作用同时有效地被完全掩蔽，且该口服固体制剂可直接服用，即使根据需要添加制剂添加物，调制成细粒剂、颗粒剂、片剂、胶囊剂、口腔内崩解片等剂型，异丁苯丙酸的苦味和粘膜刺激性的掩蔽作用也不会有损。此外，本发明的口服固体制剂可根据各剂型的需要，添加香料、矫味剂和甜味剂等，这样便于掩蔽咖啡因的苦味。
具体实施方式
以下，对本发明进行更详细的说明。
用于本发明的异丁苯丙酸只要符合日本药典第14次修正版即可，无特别限定，但为了有效地进行掩蔽，异丁苯丙酸的平均粒径较好为50～500μm，更好为150～350μm。本说明书中的平均粒径是指按照以下的方法测得的测定值。
通过电磁式振动筛M-2型(筒井化学机械株式会社)，采用JIS标准筛(Z8801-1987)，对10g试样进行15分钟的筛分，籍此测定质量％基准的粒度分布，将累计质量分布达到50％时的粒径作为平均粒径进行计算。
该平均粒径的异丁苯丙酸如果能够获得即可直接使用，如果不是这样的情况，则最好进行过筛或粉碎、造粒等，调整异丁苯丙酸的粒径后再使用。
用于本发明的咖啡因只要符合日本药典第14次修正版即可，可使用咖啡因、无水咖啡因和苯甲酸钠咖啡因中的任一种。用于本发明的咖啡因的粒径最好小于异丁苯丙酸的粒径。即，咖啡因的平均粒径较好为1～180μm，更好为1～100μm。该平均粒径的咖啡因如果能够获得即可直接使用，如果不是这样的情况，则最好进行过筛或粉碎、造粒等，调整咖啡因的粒径后再使用。
此外，咖啡因的掺入量因异丁苯丙酸和咖啡因的各自的粒径而异，通常相对于100质量份异丁苯丙酸，咖啡因的掺入量较好为5～500质量份，特好为10～100质量份，更好为45～60质量份。
用于本发明的结晶纤维素只要是被用于制剂的结晶纤维素即可，无特别限定。作为市售品，可例举アビセル(FMC化学公司)、セオラス(旭化成化学株式会社)等。结晶纤维素的掺入量相对于100质量份的异丁苯丙酸，通常较好为1～5000质量份，特好为2～20质量份，更好为5～8质量份。
用于本发明的水溶性高分子只要是可溶于精制水的高分子即可，无特别限定。作为该水溶性高分子，可例举羟丙基纤维素、羟丙基甲基纤维素、羧甲基纤维素钠、甲基纤维素、阿拉伯树胶、聚乙烯吡咯烷酮、糊精、褐藻酸钠、酪蛋白等，上述水溶性高分子可1种单独使用或2种以上混合使用。其中，较好的是羟丙基纤维素、羟丙基甲基纤维素、羧甲基纤维素钠、甲基纤维素、聚乙烯吡咯烷酮，特好为羟丙基纤维素。本发明中，相对于100质量份异丁苯丙酸，水溶性高分子的掺入量通常为0.1～8000质量份，特好为0.5～10质量份，更好为1～3质量份。
(制备方法)
本发明的口服固体制剂可通过将异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子湿式造粒后进行干燥而制得。
湿式造粒时最好采用精制水或含醇水溶液。此时，可将水溶性高分子的一部分或全部溶于精制水或含醇水溶液中再使用。作为含醇水溶液中所用的醇，可例举乙醇、异丙醇等低级醇，特好为乙醇。此外，醇/水的质量比较好为0/100～80/20。造粒时，可一次性地将异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子一起进行湿式造粒，也可将异丁苯丙酸、咖啡因及水溶性高分子湿式造粒后，再添加结晶纤维素然后进行湿式造粒，或者添加异丁苯丙酸及水溶性高分子进行湿式造粒后，再添加咖啡因及结晶纤维素然后进行湿式造粒。这种情况下，作为造粒方法，可例举搅拌造粒、挤压造粒法、喷雾造粒法、流动造粒法、滚动造粒法、滚动流动造粒法等公知的湿式造粒法。
对异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子进行湿式造粒时，可仅掺合这些成分进行湿式造粒，还可以在无损本发明的效果的前提下，根据需要添加后述的药理活性物质或制剂添加物等进行湿式造粒。
本发明对造粒后的干燥方法无特别限定。例如，可采用流化床干燥机、箱型干燥机等通过常规方法进行干燥。此外，加热温度最好根据异丁苯丙酸、咖啡因及其它掺入的药理活性物质的热稳定性进行调整，通常较好为25～60℃，特好为45～50℃。较好的是干燥进行至利用干燥减量(50℃，10分钟)的水分测定达到3％以下的程度，特好的是达到1％以下的程度。
本发明的口服固体制剂可直接使用，也可根据需要添加其它的药理活性物质或制剂添加物，调制成细粒剂、颗粒剂，或进一步将造粒物调制成片剂、口腔内崩解片、包衣片、糖衣片、胶囊剂等。此外，可根据各剂型的要求，添加甜味剂、矫味剂、清凉化剂、着色剂、着香剂、香料、芳香剂等，这样可掩蔽咖啡因的苦味。
作为可加入本发明的口服固体制剂的药理活性物质，可例举阿司匹林、异丙基安替比林、扑热息痛、乙柳酰胺、水杨酰水杨酸、水杨酰胺、水杨酸、双吡苯丙酸、美洛昔康、洛索洛芬等解热·镇痛药，烯丙基异丙基乙酰脲、溴异戊酰脲等镇静剂，苯海拉明、吡氯苄氧胺、异丁嗪、扑尔敏、甲喹吩嗪、氯苯苄咯、依匹斯汀等抗组胺药物，双噻甲哌啶、美沙芬、可待因、双氢可待因、那可丁、甲基麻黄碱、假麻黄碱、苯福林等镇咳药及兴奋剂，福多司坦、愈甘醚、碘化钾、溴己胺、羧甲司坦、氨溴醇、茶碱、1-薄荷醇等去痰药，维生素B1及其衍生物、维生素B2及其衍生物、维生素C、橙皮甙、维生素A及其衍生物、维生素E及其衍生物等维生素类，麻黄、南天果实、樱皮、远志、甘草、桔梗、车前子、石蒜、远志、贝母、茴香、黄连、莪述、洋甘菊花、桂皮、龙胆、牛黄、动物胆、沙参、生姜、苍术、丁香、陈皮、白术、地龙、竹节人参、人参、黄岑、葛根、杏仁、香附子、梗米、厚扑、五味子、柴胡、细辛、芍药、苏叶、大枣、麦门冬、半夏、茯苓、葛根汤、桂枝汤、香苏散、柴胡桂枝汤、小柴胡汤、小青龙汤、麦门冬汤、半夏厚扑汤、麻黄汤、荆芥、连翘、辛夷、桃仁、附子等生药末及其浸膏，氨基乙酸、氧化镁、碳酸镁、硅酸镁、合成硅酸铝、合成铝碳酸镁、二氢化铝·氨基乙酸盐、氢氧化铝凝胶、干燥氢氧化铝凝胶、氢氧化铝·碳酸镁混合干燥凝胶、氢氧化铝·碳酸氢钠共沉物、氢氧化铝·碳酸钙·碳酸镁共沉物、氢氧化镁·硫酸铝钾共沉物、硅铝酸镁、氢氧化镁、硫酸铝、胃溃宁等产酸剂或粘膜保护剂，菠萝蛋白酶、链霉蛋白酶、沙雷肽酶、半碱性蛋白酶、链激酶、链道酶、氯化溶菌酶等消炎酶药物等，它们可根据需要1种或2种以上掺合使用。
作为可加入本发明的口服固体制剂的制剂添加物，例如可例举赋形剂、粘合剂、崩解剂、崩解助剂、润滑剂、表面活性剂、还原剂、缓冲剂、吸附剂、流动化试剂、防静电剂、涂剂、增塑剂、防粘附剂、遮光剂、光泽化剂、抗氧化剂、甜味剂、矫味剂、清凉化剂、着色剂、着香剂、香料、芳香剂等。在不影响到本发明的效果的前提下，可根据需要单独使用上述制剂添加物也可数种组合掺入。
作为可掩蔽咖啡因的苦味的矫味剂、清凉化剂、着香剂、香料、芳香剂、甜味剂的具体例，可例举薄荷、药用鼠尾草、草莓、月桂叶、生姜、樱桃、橙、浆果、杂交水果、葡萄、肉桂、茴香、丁香、日本种薄荷、豆蔻、花椒、辣椒、薄荷浸膏、薄荷醇、5’-肌苷酸二钠、5-鸟苷酸二钠、DL-丙氨酸、dl-樟脑、dl-薄荷醇、dl-苹果酸、dl-苹果酸钠、DL-酒石酸钠、d-樟脑、D-木糖、D-酒石酸、L-天冬氨酸、L-天冬氨酸钠、L-天冬氨酸镁、L-谷氨酸、L-谷氨酸L-精氨酸、L-谷氨酸钠、L-谷氨酸盐酸盐、1-薄荷醇、β-环糊精、抗坏血酸、天冬甜素、棕儿茶末、土常山、土常山浸膏、土常山末、氨基乙磺酸、茴香、茴香酊剂、茴香末、茴香油、乙醇、乙基香草醛、赤藓醇、黄柏末、雌黄末、黄连、黄连末、刺芒柄花根干燥浸膏、橙、橙油、可可末、桑果浸膏、焦糖、碳酰胆碱、甘草、甘草浸膏、甘草粗浸膏、甘草末、木糖醇、柠檬酸、柠檬酸钙、柠檬酸钠、甘氨酸、甘油、甘草酸、甘草酸二铵、甘草酸二钾、甘草酸二钠、甘草酸铵、甘草酸三钠、葡糖酸-δ-内酯、小球藻浸膏、小球藻末、肉桂酊剂、肉桂末、肉桂油、琥珀酸、琥珀酸二钠六水合物、琥珀酸钠、海带末、糖精、糖精钠、藏红花、藏红花酊剂、山椒酊剂、山椒末、砂仁末、生姜酊剂、生姜末、生姜油、沉香末、肉桂醛、硬脂酸、薄荷油、当药、紫苏末、大豆油、大枣末、蒲公英根·草干燥浸膏、鞣酸、丁香酊剂、丁香油、陈皮酊剂、辣椒、辣椒末、辣椒酊剂、橙皮酊剂、橙皮末、苦木末、凤梨粉末香料 51357、凤梨粉末香料 59492、蜂蜜、薄荷水、薄荷油、香草粉末香料 5428632、焦磷酸四钠、葡萄酒、葡萄糖、葡萄糖果糖液糖、富马酸、富马酸钠、薄荷粉末、聚乙烯吡咯酮、麦芽糖醇、麦芽糖醇液、麦芽糖、麦芽醇、甲基纤维素、薄荷醇粉末、桉树油、龙脑、龙脑末、林格液、苹果果汁、苹果酸、苹果浓缩果汁(500％)、柠檬油、玫瑰水、玫瑰油、蜂王浆、液糖、氯化钠、氯化镁、盐酸、果糖、果糖葡萄糖液糖、干燥酵母、还原麦芽糖、水饴、稀盐酸、高葡萄糖水饴、高果糖液糖、黑砂糖、酒石酸、酒石酸氢钠、食用胡萝卜末、乙酸、水饴、精制甘草末、精制蜂蜜、精制白糖、精制白糖球状颗粒、脱脂奶粉、单糖糖浆、碳酸氢钠、中链脂肪酸三甘油酯、叶绿酸钠铜、乳酸、乳糖、浓甘油、梅子浸膏、甜味素、甜叶菊甜味剂、蔗糖聚络合物、乙酰磺胺酸钾K(安赛密K)、阿力甜、冰醋酸、糖粉、粉末还原麦芽糖水饴、无水乙醇、柠檬酸酐、无水焦磷酸钠、丁酸乙酯、绿茶末等。在不影响到本发明的效果的前提下，上述材料可单独使用或多种组合使用。
以下，根据实施例对本发明进行更详细地说明，但本发明并不仅限于下述
实施例。
[实施例1]
颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、640g无水咖啡因(平均粒径76μm)、80g结晶纤维素(セオラスPH-101，旭化成化学株式会社制)和20g羟丙基纤维素(HPC-L微粉，日本曹达株式会社制)，用高速搅拌造粒机(FM-VG-10，パウレック公司制)进行搅拌后，慢慢地添加320g精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得实施例1的颗粒剂。
[比较例1]
比较例1的颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、640g玉米淀粉、80g结晶纤维素(セオラスPH-101)和20g羟丙基纤维素(HPC-L微粉)，用高速搅拌造粒机(FM-VG-10)进行搅拌后，慢慢地添加320g精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得比较例1的颗粒剂。
[比较例2]
比较例2的颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、640g无水咖啡因(平均粒径76μm)、80g乳糖和20g羟丙基纤维素(HPC-L微粉)，用高速搅拌造粒机(FM-VG-10)进行搅拌后，慢慢地添加320g精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得比较例2的颗粒剂。
[比较例3]
比较例3的颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、640g无水咖啡因(平均粒径76μm)和80g结晶纤维素(セオラスPH-101)，用高速搅拌造粒机进行搅拌后，在其中慢慢地添加320g精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得比较例3的颗粒剂。
[比较例4]
比较例4的制剂的制备：
称量120g异丁苯丙酸(平均粒径248μm)、64g无水咖啡因(平均粒径76μm)、8g结晶纤维素和2g羟丙基纤维素，将它们均一地混合，获得比较例4的制剂。
[实施例2]
颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、666.6g无水咖啡因(平均粒径76μm)、80g结晶纤维素和20g羟丙基纤维素，用高速搅拌造粒机进行搅拌后，慢慢地添加240g的60％乙醇水溶液，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得实施例2的颗粒剂。
[实施例3]
颗粒剂的制备：
称量1200g异丁苯丙酸(平均粒径248μm)、400g无水咖啡因(平均粒径76μm)、80g结晶纤维素和20g羟丙基纤维素，用高速搅拌造粒机进行搅拌后，慢慢地添加300g的精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，获得实施例3的颗粒剂。
[试验例1]
用5名受试者，按照下述基准进行实施例1～3、比较例1～4获得的颗粒的苦味和刺激作用的评价。结果示于表1。
苦味：++表示相当苦，+表示苦，±表示略苦，-表示不苦
刺激：++表示对喉部具有相当的刺激感，+表示对喉部有刺激，±表示对喉部略有刺激，-表示对喉部无刺激。
表1
| 1 | 2 | 3 | 4 | 5 | ||
| 实施例1 | 苦味 | ± | - | + | ± | - |
| 刺激 | - | ± | + | - | - | |
| 实施例2 | 苦味 | ± | - | + | + | ± |
| 刺激 | - | ± | ± | - | - | |
| 实施例3 | 苦味 | ± | + | - | ± | + |
| 刺激 | - | - | ± | - | - | |
| 比较例1 | 苦味 | ++ | ++ | ++ | ++ | ++ |
| 刺激 | ++ | ++ | ++ | ++ | ++ | |
| 比较例2 | 苦味 | + | ++ | ++ | ++ | ++ |
| 刺激 | ++ | + | ++ | ++ | ++ | |
| 比较例3 | 苦味 | + | + | ++ | ++ | ++ |
| 刺激 | ++ | + | ++ | ++ | ++ | |
| 比较例4 | 苦味 | ++ | + | ++ | ++ | ++ |
| 刺激 | ++ | + | ++ | ++ | ++ |
从表1的结果可确认，本发明的口服固体制剂可抑制异丁苯丙酸的苦味的同时，其对于粘膜刺激作用的抑制效果明显。
[实施例4]
颗粒剂的制备：香料添加
称量3000g异丁苯丙酸(平均粒径248μm)、1600g咖啡因(平均粒径76μm)、200g结晶纤维素、50g羟丙基纤维素(HPC-L微粉，日本曹达株式会社制)，用高速搅拌造粒机(FM-VG-25，パウレック公司制)进行搅拌后，慢慢地添加800g精制水，进行混炼·造粒。于50℃利用流化床干燥机对造粒物进行1小时的干燥后过筛，在100g该颗粒剂中混入1g柑橘香料，获得实施例4的颗粒剂。
[实施例5]
颗粒剂的制备：添加香料和矫味剂
在100g实施例4获得的颗粒中混入0.25g甜味素、0.25g安赛密K、1.5g柠檬酸、1g富马酸、1g柑橘香料，获得实施例5的颗粒剂。
[试验例2]
用5名受试者，按照下述基准进行实施例4和5获得的颗粒的苦味和刺激作用的评价。结果示于表2。
苦味：++表示相当苦，+表示苦，±表示略苦，-表示不苦
刺激：++表示对喉部具有相当的刺激感，+表示对喉部有刺激，±表示对喉部略有刺激，-表示对喉部无刺激。
表2
| 1 | 2 | 3 | 4 | 5 | ||
| 实施例4 | 苦味 | - | ± | - | ± | - |
| 刺激 | - | ± | - | - | - | |
| 实施例5 | 苦味 | - | - | - | - | - |
| 刺激 | - | - | - | ± | - |
从表2的结果可确认，本发明的口服固体制剂可抑制异丁苯丙酸的苦味的同时，其对于粘膜刺激作用的抑制效果明显。此外，由于添加了香料、矫味剂，所以也能够抑制咖啡因的苦味。
[实施例6]
将实施例4获得的颗粒1000g每次242.5mg填入硬胶囊中，获得胶囊剂。
本发明的口服固体制剂的异丁苯丙酸的苦味和粘膜刺激性都得到了显著地掩蔽，利用简单且价廉的设备及工序就可制得该制剂，因此，可广泛地应用于固体制剂。
此外，本发明的口服固体制剂可直接或根据需要，再掺入药理活性物质或制剂添加物，制成细粒剂、颗粒剂、片剂、口腔内崩解片、包衣片、糖衣片、胶囊剂等，作为生理疼痛、头痛、偏头痛、牙痛、咽喉痛、关节痛、肌肉痛、神经痛、腰痛、肩胛痛、拔牙后的疼痛、跌打痛、耳痛、骨折痛、扭伤痛、外伤痛的镇痛、寒颤·发热时的解热的治疗的解热·镇痛剂使用，或者作为缓解感冒的各种症状(喉部的疼痛、发热、寒颤、头痛、流涕、鼻塞、打喷嚏、咳嗽、痰、关节的疼痛、肌肉的疼痛)的感冒药使用。
Claims (6)
1.口服固体制剂，其特征在于，将异丁苯丙酸、咖啡因、结晶纤维素和水溶性高分子湿式造粒后进行干燥而得。
2.如权利要求1所述的口服固体制剂，其特征在于，水溶性高分子为选自羟丙基纤维素、羟丙基甲基纤维素、羧甲基纤维素钠、甲基纤维素、阿拉伯树胶、聚乙烯吡咯烷酮、糊精、褐藻酸钠、酪蛋白的1种或2种以上。
3.如权利要求1所述的口服固体制剂，其特征在于，异丁苯丙酸是平均粒径为50～500μm的粉末。
4.如权利要求1所述的口服固体制剂，其特征在于，咖啡因是平均粒径1～180μm的粉末。
5.如权利要求1所述的口服固体制剂，其特征在于，异丁苯丙酸、咖啡因、结晶纤维素及水溶性高分子的比例是100∶5～500∶1～5000∶0.1～8000质量份。
6.口服固体制剂的制备方法，其特征在于，将异丁苯丙酸、咖啡因、结晶纤维素和水溶性高分子湿式造粒后进行干燥。
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|---|---|---|---|---|
| JPH09208458A (ja) * | 1996-02-02 | 1997-08-12 | Ss Pharmaceut Co Ltd | 不快な味がマスキングされた製剤 |
| US5904937A (en) * | 1997-10-03 | 1999-05-18 | Fmc Corporation | Taste masked pharmaceutical compositions |
| JPH11193230A (ja) * | 1997-12-26 | 1999-07-21 | Takeda Chem Ind Ltd | 放出制御製剤 |
| JP5248733B2 (ja) * | 2003-11-28 | 2013-07-31 | エスエス製薬株式会社 | 揮散防止型固形製剤およびその製造方法 |
-
2005
- 2005-11-09 JP JP2005324968A patent/JP2007131561A/ja active Pending
-
2006
- 2006-11-01 KR KR1020060107016A patent/KR20070049962A/ko not_active Application Discontinuation
- 2006-11-08 CN CN200610146455XA patent/CN1965836B/zh not_active Expired - Fee Related
-
2007
- 2007-07-26 HK HK07108113.8A patent/HK1100352A1/xx not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105249439A (zh) * | 2015-11-10 | 2016-01-20 | 朱丽芬 | 一种具有抗氧化功能的粘性糖粉 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20070049962A (ko) | 2007-05-14 |
| CN1965836B (zh) | 2011-02-02 |
| JP2007131561A (ja) | 2007-05-31 |
| HK1100352A1 (en) | 2007-09-21 |
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