CN100404073C - 一种难溶性药物凝胶制剂制备方法 - Google Patents
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Abstract
本发明涉及一种难溶性药物凝胶制剂制备方法。该凝胶剂的生理活性物质为难溶性药物，其制备方法特征为在凝胶的制备过程中加入亲水性物质，增大主药在水中的溶解度，使主药在凝胶中分散均匀，凝胶稳定性良好。
Description
技术领域
本发明涉及以难溶性药物为生理活性物质的凝胶制备方法。
技术背景
难溶性药物红霉素(Erythromycin)、氯霉素(Chloramphenicol)、阿奇霉素(Azithromycin)、酮康唑(Ketoconazole)、联苯苄唑(Bifonazole)等抗菌类难溶性药物制成外用制剂，不仅避免了口服给药存在的胃肠道首过效应，而且使副作用大大减少。但是，由于乳膏剂的皮肤涂附舒适性差，而凝胶剂具有更易于涂展和洗除、无油腻感、同时能够吸收组织渗出液、不妨碍皮肤正常功能等优点，所以将难溶性药物制备成凝胶制剂具有更广泛的发展空间。难溶性药物在基质中溶解量低，不易分散均匀。因此，制备难溶性药物凝胶剂应考虑改善难溶性药物在基质中的溶解和均匀分散性。
本发明是基于改善上述技术中存在的问题而提出的，其目的是提供一种难溶性药物凝胶剂的制备方法。
本发明者为了达到上述目的，进行了反复深入的研究和试验，结果发现在凝胶制备过程中加入亲水性物质，可增大难溶性药物在基质中的溶解，使得生理活性物质在凝胶中分散均匀，凝胶稳定性良好。
实施发明的技术措施
本发明涉及一种难溶性药物凝胶制备方法。由于难溶性药物在凝胶基质中溶解量低，不易分散，因此，在该凝胶制剂制备过程中加入了有助于难溶性药物溶解的亲水性物质，从而增大生理活性物质在凝胶中的溶解，制备分散均匀、稳定性良好的凝胶。
本发明的生理活性成分为难溶性药物，可以为红霉素、氯霉素、阿奇霉素、酮康唑、联苯苄唑，优选抗菌类难溶性药物。难溶性药物的用量为0.5％-10％(重量)，优选1％-5％(重量)。
本发明中凝胶的基质包括卡波姆、羧甲基纤维素钠、甲基纤维素、羟丙基纤维素、海藻酸钠、明胶或它们的组合物，可采用改变上述物质浓度或调节pH等方法使上述基质构成的凝胶具有适宜的粘度。基质的用量为0.5％-10％(重量)，优选卡波姆，用量为0.5％-2％(重量)。
本发明中为了增大难溶性药物在水中的溶解度，在制剂制备过程中加入了亲水性物质助溶剂包括丙二醇、异丙醇、甘油、乙醇及它们的组合物。助溶剂的用量为1％-30％(重量)，优选5％-20％(重量)。
本发明中为了改善难溶性药物在基质中的分散性，在凝胶组合物中加入了亲水性物质表面活性剂，包括泊洛沙姆、十二烷基硫酸钠、聚氧乙烯脂肪酸酯及其相互混合物。在生理活性物质中加入基质前，可将其溶于亲水性物质的水溶液中进行分散乳化，再加入到凝胶基质中搅拌，分散。表面活性剂的用量为0.1％-3％(重量)，优选0.3-1.5％(重量)。
本发明在制剂组合物中除加亲水性物质包括助溶剂和表面活性剂等物质外，还可以加入其他辅料，如络合剂乙二胺四乙酸二钠；pH调节剂氢氧化钠、三乙醇胺；防腐剂对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯等。
用上述制剂制备方法制备的难溶性药物凝胶具有以下优点：凝胶细腻，稠度适宜，易于涂展，生理活性物质分布均匀，稳定性好，以及美观，容易洗除。
实施例
下面结合实施例对本发明作进一步详细说明。
结合实施例具体说明本发明，但并不局限于下述的实施例。其中“％”是指“重量％”。
对比实施例
制备工艺：
卡波姆934搅拌加入红霉素和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液，混匀，得红霉素凝胶。
实施例1
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，加入红霉素、泊洛沙姆188、丙二醇和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液、混匀，得红霉素凝胶。
实施例2
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，加入红霉素、十二烷基硫酸钠、异丙醇和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液、混匀，得红霉素凝胶。
实施例3
制备工艺：
海藻酸钠搅拌加入水中，待完全溶解后，加入泊洛沙姆188和水的混悬液，在快速搅拌的情况下，加入红霉素、对羟基苯甲酸甲酯和丙二醇的混悬液，混匀，得红霉素凝胶。
实施例4
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，在快速搅拌的情况下，加入红霉素、聚氧乙烯(40)硬脂酸酯、甘油、对羟基苯甲酸乙酯和水的混悬液，混匀，得红霉素凝胶。
实施例5
制备方法：
卡波姆940搅拌加入水中，待完全溶解后，在快速搅拌的情况下，加入氯霉素、甘油、三乙醇胺、对羟基苯甲酸乙酯和水的混悬液，混匀，得氯霉素凝胶。
实施例6
制备工艺：
卡波姆940搅拌加入水中，待完全溶解后，加入氨试液。在快速搅拌的情况下，加入酮康唑、乙醇、泊洛沙姆188、甘油和水的混悬液，混匀，得酮康唑凝胶。
如上述对比实施例制备的凝胶，难溶性药物在基质中溶解度小，分散不均匀，观察粒径部分大于180um，不符合药典附录要求；且稳定性不好，放置后有分层现象。按照本发明，实施例制备的凝胶，含有亲水性物质助溶剂，难溶性药物在基质中溶解度较大，有良好的释放、穿透性，能保证药物疗效的发挥；药物经亲水性物质表面活性剂乳化，难溶性药物在基质中分散均匀，稳定性好，贮存时无酸败、变质、分层等现象。
Claims (2)
1.一种含有红霉素的凝胶制剂，其特征在于含有占重量百分比2％的红霉素、0.9％的卡波姆、2％泊洛沙姆、10％丙二醇、0.1％乙二胺四乙酸二钠、0.38％氢氧化钠和84.62％的水，并通过将卡波姆加入乙二胺四乙酸二钠水溶液，完全溶解后，加入红霉素、泊洛沙姆、丙二醇和水的混悬液，快速搅拌下，加入氢氧化钠、混匀的方法制备得到。
2.如权利要求1凝胶制剂，其特征在于含有所述卡波姆为卡波姆934、所述泊洛沙姆为泊洛沙姆188。
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| CN1397272A (zh) * | 2002-08-19 | 2003-02-19 | 上海兴康医药研究开发有限公司 | 可滴眼用在体凝胶制剂及其制备方法 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1397272A (zh) * | 2002-08-19 | 2003-02-19 | 上海兴康医药研究开发有限公司 | 可滴眼用在体凝胶制剂及其制备方法 |
Non-Patent Citations (4)
| Title |
|---|
| 酮康唑凝胶剂的制备及临床疗效观察. 范义凤，王华.制剂技术，第12卷第4期. 2003 |
| 酮康唑凝胶剂的制备及临床疗效观察. 范义凤，王华.制剂技术，第12卷第4期. 2003 * |
| 阿奇霉素凝胶的制备及质量控制. 张国友，宣艳.中国药师，第6卷第4期. 2003 |
| 阿奇霉素凝胶的制备及质量控制. 张国友，宣艳.中国药师，第6卷第4期. 2003 * |
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| CN1676120A (zh) | 2005-10-05 |
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