CAJ | 학술논문

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 h 40°C，1～6 h 45°C，6～30 h 50°C）的方法用于介质加热，（8、13和28）×1033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。
목적건립일충여체내석약수거상관적체외가속석약평개방법，용우흉선오태미구적처방우화화질량공제。방법잔류법측정미구재대서체내적석방정황，회제체내루적석약곡선；대체외가속석방적중요조건진행사선，포괄석방개질충류、을순농도、표면활성제농도、가열온도，진행체내외석방상관성의합，최대정도모의체내석방，병채용최종우화적조건험증령량충처방。결과최종우화적체외석방조건위：20%（V/V）을순중함0.06%（W/V）Tween 80작위석방개질，정서승온（0～1 h 40°C，1～6 h 45°C，6～30 h 50°C）적방법용우개질가열，（8、13화28）×1033충상대분자질량PLGA제비적미구체외가속곡선여체내석약곡선상관계수r2의차위0.9783、0.9886화0.9780。결론석방개질중가입을순병채취정서승온적판법，능최대정도모의체내석약，가용우흉선오태미구적처방우화화질량공제。
Objective To establish an accelerated method that has good correlations with in vivo release data for formulation optimization and quality control purposes of thymopentin-loaded poly(DL-lactide-co-glycolide)(PLGA)microspheres. Methods In vivo thymopentin release from the microspheres was studied in Sprague-Dawley rats and relevant cumulative release curves were plotted. Key factors including release medium types,ethanol concentrations,surfactant concentrations and heating temperature were investigated for the in vitro accelerated release. The conditions for accelerated release were optimized to make the accelerated release cures fit the in vivo release well. The final optimized accelerated release method was validated in other two formulations. Results The final optimized accelerated release conditions were: 20% hydro-alcoholic solutions (V/V)and 0.06% Tween 80 (W/V)as the release media,gradient heating program (0-1 h at 40 °C,1-6 h at 45 °C and 6-30 h at 50 °C)as the media heating method. After fitted with the in vivo release curves,the correlation constant r2 of (8,13 and 28)×103 PLGA microspheres was 0.9783,0.9886 and 0.9780,respectively. Conclusion By introducing alcohol into the release media and applying gradient heating program,the reported accelerated method can be used in the formulation optimization and quality control of thymopentin-loaded PLGA microspheres.