罗替戈汀植入剂的制备及体外释放介质的研究

Preparation and in vitro release of rotigotine-loaded implants

目的:制备可持续缓慢释药的罗替戈汀植入剂,并进行罗替戈汀植入剂体外释放介质的筛选。方法:采用热熔挤出法制备罗替戈汀植入剂,考察其在5种释放介质中的体外释药行为,通过体内外相关性拟合筛选最优释放介质,并用于各处方植入剂的体外释放评价,进行处方筛选。结果:以PLGA 8515 5A和5050 2A混合高分子为载体材料制备的罗替戈汀植入剂可持续平稳释药达40 d。罗替戈汀植入剂体外评价的最优释放介质为p H 4.5醋酸盐缓冲液,体内外拟合相关系数r为0.997,药物释放符合扩散-溶蚀模型。结论:罗替戈汀植入剂可实现长期缓慢释药,p H 4.5醋酸盐缓冲液作为释放介质用于罗替戈汀植入剂的体外释放评价,可预测体内的释药行为,从而可用于指导制剂处方筛选及质量评价。

Objective： To prepare rotigotine-loaded implants to achieve continuous sustained release of rotigotine and to select the in vitro release medium of rotigotine-loaded implants. Methods： Rotigotine-loaded im- plants were prepared using hot-melt extrusion method and in vitro release behavior was investigated in 5 kinds of re- lease media. Based on in vitro^in vivo correlations （IVIVC） between in vitro release profile and in vivo, the optimal release medium was selected to evaluate in vitro release characteristics of implants of each prescription. Results： Rotigotine could achieve sustained release for about 40 days from the implants prepared by PLGA 8515 5A with the addition of 5050 2A. The optimal in vitro release medium of rotigotine-loaded implants was acetate buffer solution （pH 4.5） and the coefficient of IVIVC is 0. 997. The release kinetics of rotigotine from implants followed a near diffusion-corrosion release kinetics model. Conclusion： Rotigotine can achieve continuous sustained release from rotigotine-loaded implants. In vitro release evaluation of rotigotine-loaded implants in acetate buffer solution （pH 4.5） can predict in vivo release behavior, and thus can be used on prescription screening and quality control.