盐酸氨酮戊酸温敏型原位凝胶的设计与优化  

Design and optimization of thermosensitive in situ gel of 5-aminolevulinic acid hydrochloride

作　　者：曾令军[1] 庄珊珊[1] 黄爱文[1] 宋洪涛[1] ZENG Ling-jun ZHUANG Shan-shan HUANG Ai-wen SONG Hong-tao(Department of Pharmacy, Fuzhou General Hospital, Fuzhou 350025, Chin)

机构地区：[1]福州总医院药学科,福州350025

出　　处：《中国新药杂志》2017年第20期2485-2490,共6页Chinese Journal of New Drugs

摘　　要：目的:将盐酸氨酮戊酸研制成一种温敏型原位凝胶制剂。方法:以凝胶剂外观和胶凝温度为指标,优化最佳凝胶基质、保湿剂、防腐剂、透皮促渗剂和药物浓度;以药物累积透过量、稳态透皮速率、累积透过率等为指标,筛选最佳透皮促渗剂;以药物累积释放率为指标,评价优化处方体外释药特性。结果:优化的最佳处方组成为:盐酸氨酮戊酸5%,泊洛沙姆407为20%,泊洛沙姆188为4%,甘油10%,羟苯乙酯0.1%,丙二醇1%,氮酮3%,加水至100%;优化的盐酸氨酮戊酸温敏型原位凝胶透皮吸收优于市售制剂;盐酸氨酮戊酸温敏型原位凝胶4 h累积释放量达80%,释药模型符合一级动力学方程。结论:本研究制备的盐酸氨酮戊酸温敏型原位凝胶制剂具有较好的释放度和透皮吸收性,有望成为一种新型的盐酸氨酮戊酸光动力学疗法用制剂。Objective： To develop thermosensitive in situ gel of 5-aminolevulinic acid hydrochloride.Methods： Appearance and gelling temperature were used as indexes to determine the optimal gel bases,moisturizer,preservative,penetration enhancer and drug concentration.The penetration enhancer was further screened with cumulative penetration amount,steady penetration rate and cumulative transmittance as the evaluation indexes.The in vitro release property was also evaluated with accumulative release rate as the evaluation index.Results： The optimum formulation composition was confirmed as follows： 5% 5-aminolevulinic acid hydrochloride,20% poloxamer407,4% poloxamer 188,10% glycerinum,0.1% ethylparaben,1% propylene glycol,3% azone,with water added to 100%.The transdermal absorption of the optimum thermosensitive in situ gel of 5-aminolevulinic acid hydrochloride was better than the commercially available preparation.The accumulative release rate in 4 h of the prepared gel was up to 80%.The release property in vitro conformed to first order kinetic equation.Conclusion： The thermosensitive in situ gel of 5-aminolevulinic acid hydrochloride developed in this study showed good release property and transdermal absorption,which may become a new-type preparation of 5-aminolevulinic acid hydrochloride for photodynamic therapy.

关 键 词：盐酸氨酮戊酸 原位凝胶 透皮吸收 体外释放 

分 类 号：R943.4[医药卫生—药剂学] R986[医药卫生—药学]