Vudathala G K, Rogers J A
Health Protection Branch, Vanier, Ontario, Canada.
Pharm Res. 1992 Jun;9(6):759-63. doi: 10.1023/a:1015899404712.
The preparation, characteristics, and behavior of microspheres of poly(L-lactic acid) (PLA) containing griseofulvin (Gris) or Gris:phospholipid coprecipitates are described. Microspheres were spherical and increased in size from 17 microns (empty) to 30 microns, containing 22% Gris. The release of coprecipitated Gris after 60 min from 146,000 MW PLA microspheres in pH 2.0 buffer at 37 degrees C was twofold greater than that from microspheres containing pure Gris. Also, the release profile from pure Gris microspheres was 25% lower than its dissolution profile, whereas the dissolution and microspheres of Gris coprecipitate suspended in PEG 600 in hard gelatin capsules for 1 week released Gris at levels comparable to the dissolution of coprecipitate. Decreasing the MW of PLA substantially increased the release of Gris from microspheres of coprecipitate after 20 min but insignificantly from microspheres of pure Gris. These findings suggest that microsphere formulation offers some new opportunities in the development of solid dispersions which normally encounter processing difficulties.
描述了含有灰黄霉素（Gris）或Gris：磷脂共沉淀物的聚（L-乳酸）（PLA）微球的制备、特性和行为。微球呈球形，大小从17微米（空微球）增加到30微米，含有22%的Gris。在37℃下，于pH 2.0缓冲液中，146,000 MW的PLA微球在60分钟后共沉淀Gris的释放量比含有纯Gris的微球高出两倍。此外，纯Gris微球的释放曲线比其溶解曲线低25%，而悬浮于PEG 600中的Gris共沉淀物微球在硬明胶胶囊中放置1周后释放Gris的水平与共沉淀物的溶解水平相当。降低PLA的分子量在20分钟后显著增加了共沉淀物微球中Gris的释放，但对纯Gris微球的释放影响不显著。这些发现表明，微球制剂在通常面临加工困难的固体分散体开发中提供了一些新机会。
