School of Pharmacy, University of Connecticut, 69 North Eagleville Rd., Unit 3092, Storrs, CT 06269, USA.
Int J Pharm. 2011 May 16;409(1-2):178-84. doi: 10.1016/j.ijpharm.2011.02.057. Epub 2011 Mar 3.
The objective was to develop an in vitro release method for protein loaded poly(lactide-co-glycolide) (PLGA) microspheres. A modified USP apparatus 4 and sample and separate methods were compared using a microsphere formulation encapsulating a model protein, bovine serum albumin (BSA). Microsphere characteristics such as porosity, drug loading, particle size and burst release were significantly affected by the formulation parameters (i.e., phase ratio, internal aqueous phase composition and theoretical drug loading). Incomplete release of BSA was observed using the sample and separate method and this was attributed to microsphere loss during sampling. This problem was overcome using the modified USP apparatus 4 method. However, an unusual decrease in cumulative percent release was observed which was considered to be due to BSA adsorption onto the hydrophobic surfaces of the modified USP apparatus 4. Addition of SDS to the release media prevented BSA adsorption and a zero order release profile was observed. The presence of SDS did not change the microsphere degradation kinetics. The results indicate the importance of understanding protein adsorption and aggregation behavior during in vitro release testing. The USP apparatus 4 method appears to be useful for investigation of in vitro release of protein loaded microspheres.
目的是开发一种用于负载蛋白质的聚（乳酸-共-乙醇酸）（PLGA）微球的体外释放方法。使用包封模型蛋白质牛血清白蛋白（BSA）的微球制剂比较了改进的 USP 装置 4 和样品分离方法。微球的特性，如孔隙率、载药量、粒径和突释，受到制剂参数（即相比例、内部水相组成和理论载药量）的显著影响。使用样品分离方法观察到 BSA 的不完全释放，这归因于采样过程中微球的损失。使用改进的 USP 装置 4 方法克服了这个问题。然而，观察到累积百分比释放的异常下降，这被认为是由于 BSA 吸附到改进的 USP 装置 4 的疏水性表面上。在释放介质中添加 SDS 可防止 BSA 吸附，并观察到零级释放曲线。SDS 的存在不会改变微球的降解动力学。结果表明，在体外释放试验中理解蛋白质吸附和聚集行为的重要性。USP 装置 4 方法似乎可用于研究负载蛋白质的微球的体外释放。
