依匹哌唑原位凝胶植入剂的体外释放研究  

In vitro release evaluation of brexpiprazole-loaded in situ gel forming implant

作　　者：邹倩 赵春杰[1] 邱宏春 郭晓迪 ZOU Qian;ZHAO Chunjie;QIU Hongchun;GUO Xiaodi(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Prinbury Biopharm Co.Ltd.,Shanghai 201203,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]普霖贝利生物医药研发(上海)有限公司,上海201203

出　　处：《沈阳药科大学学报》2023年第9期1133-1140,共8页Journal of Shenyang Pharmaceutical University

摘　　要：目的 建立一种依匹哌唑原位凝胶植入剂的体外释放方法,研究处方在体外的释放行为和缓释机制。方法 以抗精神病依匹哌唑为模型药物,制备以聚乳酸-羟基乙酸共聚物(polylactide glycolic acid, PLGA)/醋酸异丁酸蔗糖酯(sucrose acetate isobutyrate, SAIB)为基质的原位凝胶植入剂。开发体外释放检测方法,采用多种体外释放装置研究依匹哌唑原位凝胶植入剂的释放差异,考察体外释放的影响因素。结果 依匹哌唑在酯基封端PLGA/SAIB处方下显示出低突释和释放缓慢的特征,体外释放以扩散为主,符合0级释放模型。采用分层加样的流通池法,药物在14 d可达到完全释放,释放率达(85.4±2.4)%。结论 依匹哌唑原位凝胶植入剂适合采用流通池法进行体外评价,建立的体外释放方法操作简便、可靠。同时处方在体外表现出明显的缓释效果,且释放稳定。Objective The aim of this study is to establish an in vitro release test method for brexpiprazole-loaded in situ gel forming implant.To study the in vitro release behavior and sustained release mechanism of the formulation.Methods Antipsychotic drug brexpiprazole was chosen as the model therapeutic.Prepared in situ gel forming implant formulations with polylactide glycolic acid(PLGA)/sucrose acetate isobutyrate(SAIB)as matrix and 1-methyl-2-pyrrolidinone as solvent.In vitro release detection method was developed,several commonly used IVR methods were used to conduct in vitro studies for different formulations and to screen the factors affecting the in vitro release.Results Brexpiprazole showed low initial burst and sustained release characteristics with the ester-terminated PLGA/SAIB formulations and follows to zero-order model.Brexpiprazole is released from depot mainly by diffusion.Drugs can achieve completely released(85.4±2.4)%by using continuous flow through cell with layered method.Conclusion The results demonstrated both the feasibility and reliability of USP apparatus 4 method for in vitro release testing of brexpiprazole-loaded in situ gel forming implant.Brexpiprazole-loaded in situ gel showed significant sustained and steady release in vitro.

关 键 词：体外释放 原位凝胶植入剂 依匹哌唑 流通池法 

分 类 号：R94[医药卫生—药剂学]