ABSTRACT
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. MethodsIn 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. ResultsThe 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. ConclusionBy 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.
ABSTRACT
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.