注射用伊潘立酮长效缓释微球制备和评价.docVIP

注射用伊潘立酮长效缓释微球制备和评价 　　[摘要] 目的 制备伊潘立酮的PLGA微球，并进行质量评价。 方法 建立HPLC方法测定伊潘立酮的含量；比较5种规格的PLGA作为载体材料对微球质量的影响；运用正交实验设计优化处方组成和制备工艺。 结果 PLGA的种类对伊潘立酮微球的包封率和体外释放有显著影响。按照正交设计得到优化处方制备的微球，形状圆整，平均粒径为（27.3±2.7）μm，包封率为84.4%，体外释放试验第1天累计释放17.6%，28 d的累计释放度为85.7%，释药曲线符合Higuchi释放模型。 结论 本实验制备得到的伊潘立酮微球的包封率较高，没有明显的突释，具有较好的缓释效果。 　　[关键词] 伊潘立酮；PLGA；微球；正交实验；释放曲线 　　[中图分类号] R943 [文献标识码] B [文章编号] 1673-9701（2017）06-0036-04 　　[Abstract] Objective To prepare iloperidone loaded PLGA microspheres and evaluate its pharmaceutical characters. Methods The HPLC method was established to determine the concentration of iloperidone. The effect of 5 kinds of specifications of PLGA as carrier material on the quality of the microspheres was investigated. The formulation and the preparation conditions were optimized by orthogonal tests. Results The kinds of PLGA and drug encapsulation efficiency showed significant effect on the property of the microspheres， in particular on the release rate. The best formulation was obtained according to the effects of different factors on the preparation of iloperidone microspheres. The formed microspheres were spherical with smooth surface and the average size was（27.3±2.7） μm. The drug encapsulation efficiency was 84.4%. In vitro release study revealed of 17.6% at the first day and 85.7% of drug released from PLGA microspheres in 28 d. The release kinetics of microspheres in vitro were characterized by Higuchi equation. Conclusion Iloperidone-containing PLGA microspheres are prepared successfully with high encapsulation efficiency， with no obvious sudden release and good sustained release characteristics. 　　[Key words] Iloperidone； PLGA； Microspheres； Orthogonal tests； Release curve 　　伊潘立酮（iloperidone）是一?N哌啶基苯唑衍生物，为新型的非典型抗精神病药物，主要拮抗5-羟色胺2A受体（5-HT2A）和多巴胺-2受体（D2），用于成人精神分裂症的治疗。就目前临床研究资料显示，该药安全有效，主要特点为锥体外系不良反应（EPS）少、代谢异常和体质量增加的发生率较低[1-3]。目前伊潘立酮上市剂型为普通口服制剂，患者需要长期服药和特殊护理。 　　注射用长效缓释微球可以减少患者的服药次数，具有生物利用度较高、无肝脏首过效应、血药浓度平稳和患者服药顺从性高等特点。对于精神病患者因经常出现拒服、漏服药物而导致的病情恶化现象，长效微球注射剂的出现无疑能够很好地解决