甲硝唑结肠定位微丸的体外释药机理

Release mechanism of metronidazole colon-specific pellets

目的:研究自制的甲硝唑结肠定位微丸的体外释药机理。方法:用电镜观察微丸在释药前后的变化,通过替换包衣材料来考察微丸的释药行为,通过改变释放介质的渗透压来考察微丸的体外释药特性。结果:乳糖代替HPMC包衣的微丸释药后衣膜也出现破裂;释放介质渗透压升高后微丸释药速率减慢,释药速率与膜内外渗透压差之间有较好的线性关系。结论:微丸的释药机制是介质通过外层EC膜向内渗透,内层的HPMC吸水缓慢水合、溶解,药物及丸心中的水溶性物质也随后溶解,外层EC膜在渗透压作用下发生破裂,药物在渗透压驱动作用下通过EC衣膜裂口向外扩散,从而达到延时释药的效果。

Aim： To study the release mechanism of self-prepared metronidazole colon - specific pellets. Method： Morphologica property of the pellets was observed by SEM prior-and post-release. And the release characteristics of the pellet were assessed following changes of coating polymer with lactose instead of HPMC and changes of the osmotic pressure of the dissolution media. Results： Film rupture occurred in pellets with lactose instead of HPMC in the coating formulation. Release rate of pellets was reduced with the increasing of osmotic pressure of release media. And a linear correlation was found between release rate and osmotic pressure difference between inner and outside film. Conclusion：Drug release mechanism might be due to the permeation of the media through EC film, meanwhile HPMC inside the coating layer slowly hydrated and dissolved, followed by the dissolving of drug and soluble ingredients inside pellets. When the osmotic pressure led to the rupture of EC outside film, drug driven by the osmotic pressure gap diffused through the ruptured holes, thereby achieving delayed-release.