Luan Xiaosong, Bodmeier Roland
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
Eur J Pharm Sci. 2006 Feb;27(2-3):143-9. doi: 10.1016/j.ejps.2005.09.002. Epub 2005 Oct 21.
The objective of present study was to control the delivery of leuprolide acetate using in situ forming microparticle (ISM) systems. A solution of leuprolide acetate and poly(lactide-co-glycolide) (PLGA RG 503H) or poly(lactide) (PLA R 202H) in N-methyl-2-pyrrolideone (NMP) was emulsified into an external oil phase using a two-syringe/connector system. After injection into an aqueous environment, NMP diffusion led to polymer precipitation and microparticle formation in situ. ISM-systems were characterized with respect to particle morphology and the influence of formulation and processing parameters on the in vitro release. ISM from RG 503H showed a high initial release (approximately 40%), which could be attributed to the high porosity of microparticles. The initial release could be reduced by increasing the polymer concentration, increasing the amount and viscosity of the oil phase, and decreasing the drug loading. ISM-systems from R 202H had a much lower initial release (approximately 9%) compared to that from RG 503H, which was followed by a slow and continuous drug release. In comparison to conventional microparticles prepared by a solvent evaporation method, ISM from R 202H showed a lower initial release and a more linear continuous release.
本研究的目的是利用原位形成微粒（ISM）系统来控制醋酸亮丙瑞林的释放。将醋酸亮丙瑞林与聚（丙交酯-乙交酯）（PLGA RG 503H）或聚丙交酯（PLA R 202H）在N-甲基-2-吡咯烷酮（NMP）中的溶液，使用双注射器/连接器系统乳化到外部油相中。注射到水性环境后，NMP扩散导致聚合物沉淀并原位形成微粒。对ISM系统的颗粒形态以及制剂和工艺参数对体外释放的影响进行了表征。来自RG 503H的ISM显示出较高的初始释放率（约40%），这可归因于微粒的高孔隙率。通过增加聚合物浓度、增加油相的量和粘度以及降低药物载量，可以降低初始释放率。与来自RG 503H的ISM相比，来自R 202H的ISM系统的初始释放率要低得多（约9%），随后是缓慢且持续的药物释放。与通过溶剂蒸发法制备的传统微粒相比，来自R 202H的ISM显示出较低的初始释放率和更线性的持续释放。
