抗精神病药依匹哌唑新型制剂的处方设计及体外释放研究

Prescription Design and in Vitro Release Study of a Novel Formulation of the Antipsychotic Drug Brexpiprazole

摘要: 目的：制备抗精神病药依匹哌唑原位凝胶并考察其体外释放特征。方法：以星点设计–响应面法考察载体基质的浓度、载药量、添加剂浓度对原位凝胶的固化效果、流动性、体外突释的影响；考察依匹哌唑原位凝胶初步释放机制。结果：最佳处方以NMP为有机溶剂，PLGA用量为33.781%，依匹哌唑用量为2.92%，GMS用量为1.552% (w/v)。本制剂的体外累积释放度与一级释放模型相关性较好，初步认为依匹哌唑从原位凝胶中释放主要以扩散为主。结论：制备的依匹哌唑原位凝胶长效制剂具有1个月注射一次的潜力，与依匹哌唑普通口服片剂相比可显著提高患者用药依从性，可能会为新型精神病缓释制剂的开发提供一定的参考。

Abstract: Objective: To prepare in situ gel of antipsychotic drug Brexpiprazole and investigate its in vitro release characteristics. Methods: The effects of carrier matrix concentration, drug loading, and additive concentration on the curing effect, fluidity, and in vitro burst release of in situ gel were investigated by star point design-response surface methodology. The preliminary release mechanism of Brexpiprazole in situ gel was also investigated. Results: The optimal prescription was as follows: NMP as the organic solvent, PLGA dosage of 33.781%, Brexpiprazole dosage of 2.92%, and GMS dosage of 1.552% (w/v). The in vitro cumulative release of this preparation was well correlated with the first-order release model. It was preliminarily considered that the release of Brexpiprazole from in situ gel was mainly by diffusion. Conclusion: The prepared Brexpiprazole in situ gel sustained-release formulation has the potential for once-monthly injection. Compared with the common oral tablets of Brexpiprazole, it can significantly improve the medication compliance of patients and may provide certain references for the development of new sustained-release formulations for mental disorders.