奥曲肽微球-凝胶复合体系的制备及加速释放

Preparation and Accelerated Release of Octreotide Microsphere Gel Composite System

本研究旨在解决奥曲肽微球前期释放过程中的突释,将其设计成可注射的微球-凝胶复合体系。采用乳化溶剂挥发法制备奥曲肽微球,使用Box-Behnken响应面法对凝胶基质处方参数进行优化。通过考察pH、乙腈和乙醇浓度对该复合体系释药的影响,确定体外加速释放的条件,建立凝胶微球的体外加速释放方法。确定最优处方为:PL188、PL407和HPMC的质量分数分别为3%、22.2%和1%,成胶温度为37℃。该复合体系可有效减少微球前期突释,使药物释放行为更加稳定。确定体外加速释放条件为:含3%乙腈、6%乙醇、pH为7.4的PBS缓冲液为释放介质。该体外加速释放方法可快速有效评价复合体系的释放行为。

The aim of this study is to solve the burst release of octreotide microspheres in the early release process,and to design an injectable microsphere gel composite system.Octreotide microspheres are prepared by emulsion solvent evaporation method.The formulation parameters of gel matrix are optimized by Box-Behnken response surface methodology.By investigating the effects of pH,acetonitrile and ethanol concentration on the release of the composite system,we determine the conditions for accelerated release in vitro and establish an accelerated release method for Gel Microspheres in vitro.The optimum formula is as follows:PL188 mass fraction is 3%,PL407 mass fraction is 22.2%,HPMC mass fraction is 1%,and the gelling temperature is 37℃.The composite system can effectively reduce the sudden release of microspheres in the early stage and make the drug release behavior more stable.The in vitro accelerated release conditions are determined as follows:PBS buffer containing 3%acetonitrile,6%ethanol and pH 7.4 is used as the release medium.The in vitro accelerated release method could quickly and effectively evaluate the release behavior of the composite system.