pH敏感时滞型Combretastatin A4磷酸酯二钠结肠定位片的制备

Preparation of pH-time dependent colon-targeted tablet of Combretastatin A4 phosphate

目的制备pH敏感时滞型CA4P结肠靶向片(CA4P-CT)。方法以一定比例的EC和PEG6000为时滞型材料,采用压制包衣法制备时滞层,以肠溶丙烯酸树脂Ⅱ、Ⅲ为pH敏感层材料,采用喷雾包衣法制备pH敏感层。结果当EC-PEG6000(8∶1)、压制包衣后片子硬度为14.340 kg.cm-1时,时滞层可控制药物在人工肠液中4 h后释药;pH敏感层增重5%,可保证靶向片的时滞不受胃排空的影响。结论通过调整时滞层材料比例、压制包衣片硬度及肠溶层包衣厚度,包衣片可基本达到结肠定位释药的预期效果。

OBJECTIVE To prepare the pH-time dependent Colon-targeted tablet of Combretastatin A-4 phosphate（CA4P-CT）.METHODS The time layer was prepared with a certain percent of EC and PEG6000 by direct compression.The pH sensitive layer was prepared with Eudragit Ⅱand Eudragit Ⅲ by sparying coating technique.RESULTS The drug in the core tablets with time layer did not release until 4 hours in the small intestine medium when the proportion of EC and PEG-6000 was 8：1 and hardness of the tablets was 14.340 kg·cm^-1.The release was not influenced by gastric emptying when the pH-sensitive layer was weighted at 5%.CONCLUSION The pH-time dependent Colon-targeted tablets can achieve expected effect of positioning release in the colon through regulating the proportion of EC and PEG-6000,the hardness of the tablets with time layer and the coating thickness of pH-sensitive layer.