Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Republic of Korea.
Int J Pharm. 2010 Aug 30;396(1-2):91-8. doi: 10.1016/j.ijpharm.2010.06.016. Epub 2010 Jun 15.
Microcrystals of megestrol acetate (MA), a poorly water-soluble drug, were successfully prepared using an antisolvent precipitation technique for improving the dissolution rate. The effective hydrophilic polymers and surfactants used were screened for their abilities to produce smaller particle sizes. Raw micronized MA and processed MA microcrystals were ranked by the Student-Newman-Keuls test in order of increasing particle size and SPAN values as follows: processed MA microcrystals in the presence of polymer and surfactant (mean diameter 1048nm)<processed MA microcrystals in the presence of polymer (1654nm)<processed MA microcrystals in the absence of polymer and surfactant (3491nm)<raw micronized MA (4352nm). The order of BET surface area was reversely ranked. Processed MA microcrystals in the presence of polymer and surfactant slightly decreased crystallinity and altered crystal habit and preferred orientation without change in polymorph. In addition, the dissolution properties of the processed MA microcrystals in the presence of polymer and surfactant were significantly enhanced as compared to that of the raw micronized MA. This effect is mainly due to a reduction in particle size resulting in an increased surface area. Therefore, it was concluded that the antisolvent precipitation technique in mild conditions could be a simple and useful technique to prepare poorly water-soluble drug particles with reduction in particle size, a narrow particle size distribution and enhanced dissolution properties.
采用抗溶剂沉淀技术成功制备了醋酸甲地孕酮（MA）微晶，以提高其溶解速率。筛选了有效的亲水性聚合物和表面活性剂，以考察其产生更小粒径的能力。采用学生-纽曼-凯尔斯检验法对原微粉化 MA 和加工后的 MA 微晶进行排序，按粒径和 SPAN 值依次增大，结果如下：存在聚合物和表面活性剂的加工 MA 微晶（平均粒径 1048nm）<存在聚合物的加工 MA 微晶（1654nm）<无聚合物和表面活性剂的加工 MA 微晶（3491nm）<原微粉化 MA（4352nm）。BET 比表面积的顺序则相反。存在聚合物和表面活性剂的加工 MA 微晶略微降低了结晶度，改变了晶体习性和择优取向，但没有改变多晶型。此外，与原微粉化 MA 相比，存在聚合物和表面活性剂的加工 MA 微晶的溶解性能显著提高。这种效果主要归因于粒径减小导致表面积增加。因此，可以得出结论，在温和条件下采用抗溶剂沉淀技术是一种简单而有用的技术，可以制备粒径减小、粒径分布较窄且溶解性能增强的难溶性药物颗粒。
