甲氨蝶呤温敏凝胶的处方优化与体外释药特性研究

Formulation Optimization and in vitro Release Property Study of Methotrexate Thermosensitive Hydrogels

目的:优化甲氨蝶呤温敏凝胶的处方,并研究其体外释药特性。方法:以聚乳酸-羟基乙酸共聚物/聚乙二醇/聚乳酸-羟基乙酸共聚物(PLGA-PEG-PLGA)为基质,以甘露醇为黏度调节剂,制备甲氨蝶呤温敏凝胶。以胶凝温度与35℃偏差的绝对值为指标,以PLGA-PEG-PLGA、甲氨蝶呤及甘露醇的浓度为因素,通过正交试验优化其处方。采用透析袋法考察甲氨蝶呤温敏凝胶和甲氨蝶呤溶液的体外累积释放度。结果:最优处方为PLGA-PEG-PLGA浓度20%、甲氨蝶呤0.10%、甘露醇0.10%。所制备的3批甲氨蝶呤温敏凝胶的胶凝温度分别为35.1、35.0、35.0℃,平均载药率均达90%以上,12 d的累积释放度达90%以上(r=3),而甲氨蝶呤溶液240 h时已基本释放完全。结论:成功制得具有缓释作用的甲氨蝶呤温敏凝胶,且工艺简单可行。

OBJECTIVE：To optimize the formulation of Methotrexate thermosensitive hydrogels,and to study the in vitro release property of it. METHODS：Taking PLGA-PEG-PLGA as matrix and mannitol as viscosity modifiers,Methotrexate thermosensitive hydrogels were prepared. Using the absolute value of the deviation of gelation temperature between 35 ℃,its formulation was optimized by orthogonal test using the concentrations of PLGA-PEG-PLGA,methotrexate and mannitol as factors. The dialysis bag method was used to investigate accumulative release rate of Methotrexate thermosensitive hydrogels and methotrexate solution within 336 h in vitro. RESULTS：The optimal formulation was as PLGA-PEG-PLGA of 20%,methotrexate of 0.10% and mannitol of 0.10%;gelation temperature were 35.1,35.0,35.0 ℃. The average drug-loading rate was more than 90%. 12 d accumulative release rate was more than 90%（r=3）. Methotrexate solution has been substantially completely relased within 240 h. CONCLUSIONS：Methotrexate thermosensitive hydrogels with sustained-release are prepared successfully,and the preparation technology is simple and practical.