Bodmeier R, Chen H G
College of Pharmacy, University of Texas, Austin 78712-1074.
J Pharm Sci. 1989 Oct;78(10):819-22. doi: 10.1002/jps.2600781008.
Biodegradable pellets intended for either parenteral or oral use were successfully prepared from low molecular weight poly(DL-lactide) (low MW PLA, MW' = 2000) or a relatively high molecular weight poly(L-lactide) (L-PLA, MW = 215,000) sample by a simple direct compression technique without the use of heat or organic solvents. The energy imparted during the compression step caused fusion of the low MW PLA particles. Pellets prepared from low MW PLA swelled considerably before eroding in pH 7.4 buffer, but acted as an enteric matrix in 0.1 M HCl. This was attributed to the high carboxyl endgroup:polymer chain ratio which increased with a decrease in molecular weight. Interactions between salts of basic drugs (quinidine sulfate or propranolol hydrochloride) and the polymeric carboxyl endgroups caused retardation in the drug release from low MW PLA pellets. The drug release from L-PLA pellets was independent of the pH of the dissolution media and drug-polymer interactions were absent. The drug release could be increased by admixing sodium chloride prior to compression, or reduced by dipping the pellets into methylene chloride for a short period of time.
通过简单的直接压缩技术，无需加热或使用有机溶剂，成功地从低分子量聚（DL-丙交酯）（低MW PLA，MW' = 2000）或相对高分子量的聚（L-丙交酯）（L-PLA，MW = 215,000）样品制备了用于肠胃外或口服的可生物降解微丸。压缩步骤中施加的能量导致低MW PLA颗粒融合。由低MW PLA制备的微丸在pH 7.4缓冲液中侵蚀之前会显著膨胀，但在0.1 M HCl中起肠溶基质的作用。这归因于随着分子量降低而增加的高羧基端基：聚合物链比率。碱性药物（硫酸奎尼丁或盐酸普萘洛尔）的盐与聚合物羧基端基之间的相互作用导致低MW PLA微丸中药物释放延迟。L-PLA微丸的药物释放与溶解介质的pH无关，并且不存在药物-聚合物相互作用。通过在压缩前混合氯化钠可以增加药物释放，或者通过将微丸短时间浸入二氯甲烷中来减少药物释放。
