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目的建立一种与体内释药数据相关的体外加速释药评价方法,用于胸腺五肽微球的处方优化和质量控制。方法残留法测定微球在大鼠体内的释放情况,绘制体内累积释药曲线;对体外加速释放的重要条件进行筛选,包括释放介质种类、乙醇浓度、表面活性剂浓度、加热温度,进行体内外释放相关性拟合,最大程度模拟体内释放,并采用最终优化的条件验证另两种处方。结果最终优化的体外释放条件为:20%(V/V)乙醇中含0.06%(W/V)Tween 80作为释放介质,程序升温(0~1 h40°C,1~6 h 45°C,6~30 h 50°C)的方法用于介质加热,(8、13和28)×103 3种相对分子质量PLGA制备的微球体外加速曲线与体内释药曲线相关系数r2依次为0.9783、0.9886和0.9780。结论释放介质中加入乙醇并采取程序升温的办法,能最大程度模拟体内释药,可用于胸腺五肽微球的处方优化和质量控制。
OBJECTIVE: To establish an in vitro accelerated drug release evaluation method related to in vivo drug release data for prescription optimization and quality control of thymopentin microspheres. Methods Residual method was used to determine the release of microspheres in rats and the cumulative release curves were drawn. The important conditions of accelerated release in vitro were screened, including the release of media, ethanol concentration, surfactant concentration and heating temperature, Relevancy fit was released to maximize in vivo release and the other two formulations were validated using the final optimized conditions. Results The final optimized in vitro release conditions were as follows: Tween 80 containing 0.06% (W / V) Tween 80 in 20% (V / V) ethanol was used as the release medium and the temperature was programmed (0-1 h at 40 ° C for 1-6 h at 45 ° C, 6 ~ 30 h 50 ° C) for medium heating, (8, 13 and 28) × 103 PLGA preparation of microspheres in vitro acceleration curve and in vivo release curve correlation coefficient r2 were 0.9783,0.9886 And 0.9780. Conclusion The method of adding ethanol to the release medium and warming the procedure can simulate the drug release in vivo to the best extent and can be used for prescription optimization and quality control of thymopentin microspheres.