Allison S Dean
Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, Columbia, South Carolina 29208, USA.
J Pharm Sci. 2008 Jun;97(6):2022-35. doi: 10.1002/jps.21124.
Control of burst release is a major challenge in the development of poly(lactide-co-glycolide) (PLGA) microparticle drug delivery systems. It has been well-documented in previous literature that formulation and processing variables determine particle morphology, which in turn, governs drug diffusivity and burst release. However, it is not generally appreciated that PLGA polymers used for microparticle systems are typically amorphous, and as such, undergo structural relaxation during processing and storage, characterized by enthalpy and volume reduction. Volume reduction due to structural relaxation can decrease drug diffusivity within microparticles and affect burst release. The magnitude of the driving force leading to structural relaxation is linked to the rate of particle hardening, and is affected by process parameters. Studies that directly address structural relaxation in PLGA microparticles indicate that the manufacturing process and residual solvent levels, as well as the nature of the interaction between drug and polymer affect the rate of structural relaxation. Therefore, the conditions chosen for particle fabrication may be a major source of variability in the burst release and may affect the stability of the drug release profile during storage. The potential effects of structural relaxation on drug release are likely to be formulation specific. Additional work is required to understand and control the relationship between microparticle processing, structural relaxation, and performance of PLGA microparticle drug delivery systems.
控制突释是聚（丙交酯-乙交酯）（PLGA）微粒药物递送系统开发中的一项重大挑战。以往文献已充分证明，制剂和加工变量决定颗粒形态，而颗粒形态又决定药物扩散率和突释。然而，人们通常并未认识到，用于微粒系统的PLGA聚合物通常为无定形，因此在加工和储存过程中会发生结构弛豫，其特征是焓和体积减小。由于结构弛豫导致的体积减小会降低药物在微粒内的扩散率并影响突释。导致结构弛豫的驱动力大小与颗粒硬化速率相关，并受工艺参数影响。直接研究PLGA微粒结构弛豫的研究表明，制造工艺、残留溶剂水平以及药物与聚合物之间相互作用的性质会影响结构弛豫速率。因此，选择的颗粒制备条件可能是突释变异性的主要来源，并可能影响储存期间药物释放曲线的稳定性。结构弛豫对药物释放的潜在影响可能具有制剂特异性。需要开展更多工作来理解和控制微粒加工、结构弛豫与PLGA微粒药物递送系统性能之间的关系。
