5-氨基水杨酸结肠定位给药时控微丸的制备与体外释放

PREPARATION AND IN VITRO RELEASE OF 5-AMINOSALICYLIC ACID TIME CONTROLLED RELEASE PELLETS FOR COLON SPECIFIC DELIVERY

目的 用水分散体包衣技术制备 5 氨基水杨酸结肠定位微丸给药系统。方法 以低粘度HPMC为内层溶胀材料 ,乙基纤维素水分散体Aquacoat为外层控释包衣材料 ,柠檬酸三乙酯为增塑剂 ,使用流化床包衣设备 ,制备时间控制的微丸 ,用释放度测定法研究微丸在不同 pH介质中的释放度。结果 溶胀层的加入对制备时控微丸是必要的 ,药物是通过外膜破裂释放的 ,溶胀层厚度增加 ,释药时滞有一定程度的缩短 ,外层厚度增加以及增塑剂用量增加 ,可显著延长释药时滞。微丸释药随介质 pH增加而加快 ,在模拟胃肠道pH情况下延迟 5h释药 ,之后 10h内释药完全。结论 通过调整内外层的包衣厚度可制备 5 氨基水杨酸结肠定位给药微丸。

AIM To prepare 5 aminosalicylic acid (5 ASA) pellets for colon specific drug delivery with water based coating processes. METHODS 5 ASA time controlled release pellets for colon delivery were prepared in a fluid bed coater, with low viscosity HPMC as the inner swelling layer and ethylcellulose aqueous dispersion Aquacoat as the outer controlled membrane, and triethyl citrate added to the dispersion as the plasticizer. The in vitro release of pellets was investigated in different pH media and changing pH media for simulating gastrointestinal delivery. RESULTS Addition of the swelling layer was necessary for making the time controlled colon specific pellets. Drug release was triggered by rupturing the outer membrane. The lag time of drug release was shortened to a certain extent with increasing amount of swelling layer. The lag time was prolonged significantly with the increase of the thickness of the outer membrane and of the amount of the plasticizer. The data of in vitro release showed that the higher the medium pH, the faster the release of 5 ASA from pellets. The drug release was initiated after a lag time of 5 h and was completed within the following 10 h for the pellets with a 4 5% w/w HPMC coating level, a 15% w/w ethylcellulose coating level and 25% w/w plasticizer based on Aquacoat solid. CONCLUSION The time controlled pellets for 5 ASA colon specific delivery could be prepared using ethylcellulose aqueous dispersion by changing the swelling layer and controlled membrane coating levels.