School of Pharmacy, University of Connecticut, 69 North Eagleville Rd, Unit 3092, Storrs, CT 06269, USA.
Int J Pharm. 2011 Nov 28;420(2):198-205. doi: 10.1016/j.ijpharm.2011.08.035. Epub 2011 Aug 24.
The current manuscript addresses the need for a validated in vitro release testing method for controlled release parenteral microspheres. A USP apparatus 4 method was validated with the objective of possible compendial adaptation for microsphere in vitro release testing. Commercial microspheres (Risperdal Consta) were used for method validation. Accelerated and real-time release tests were conducted. The accelerated method had significantly reduced test duration and showed a good correlation with the real-time release profile (with limited number of sample analysis). Accelerated conditions were used for method validation (robustness and reproducibility). The robustness testing results revealed that release from the microspheres was not flow rate dependent and was not affected by minor variations in the method (such as cell preparation technique, amount of microspheres, flow-through cell size and size of glass beads). The significant difference in the release profile with small variations (± 0.5°C) in temperature was shown to be due to a change in risperidone catalyzed PLGA degradation in response to temperature. The accelerated method was reproducible as changing the system/equipment or the analyst did not affect the release profile. This work establishes the suitability of the modified USP apparatus 4 for possible compendial adaptation for drug release testing of microspheres.
本手稿针对需要验证控释型注射用微球的体外释放测试方法。采用 USP 装置 4 法进行验证，目的是可能将微球的体外释放测试纳入药典适应性。采用商业微球（利培酮微球）进行方法验证。进行了加速和实时释放测试。加速方法显著缩短了测试时间，并与实时释放曲线（通过有限数量的样品分析）具有良好的相关性。加速条件用于方法验证（稳健性和重现性）。稳健性测试结果表明，微球的释放不受流速影响，不受方法中的微小变化（如细胞准备技术、微球数量、流通池大小和玻璃珠大小）的影响。在温度上有微小变化（±0.5°C）时，释放曲线的显著差异表明是由于温度响应导致利培酮催化的 PLGA 降解发生变化。加速方法重现性好，改变系统/设备或分析员不影响释放曲线。这项工作证明了改良的 USP 装置 4 适用于微球药物释放测试的可能药典适应性。
