葛根芩连结肠定位片的制备工艺研究

Study on the Preparation Technology of Gegen Qinlian Colon Localization Tablet

目的:优选葛根芩连结肠定位片的最佳制备工艺。方法:根据pH和时间依赖型双重释药原理,优选葛根芩连结肠定位包衣片的最佳压片工艺和包衣工艺,通过粉末直接压片法制备定位片芯,薄膜多层包衣制备葛根芩连结肠定位片;单因素法考察包衣处方的影响因素,再采用Box-Behnken响应面法对处方进一步优化,以筛选出最佳的处方范围,并按照优化的制剂处方和制备工艺,制备结肠定位片和普通片并进行体外释放度实验研究。结果:片芯处方工艺为以浸膏粉40%,微晶纤维素26.75%,乳糖26.75%,羧甲基淀粉钠6%,硬脂酸镁0.5%进行粉末直接压片;包衣处方为从内到外依次包时滞层、肠溶层,包衣增重分别为1.0%、4.44%。时滞层处方为Eudragit RL:RS (1:2) 10 g,邻苯二甲酸二乙酯1 g,滑石粉5 g,95%乙醇200 mL;肠溶层处方为Eudragit L:S (1:5) 10 g,柠檬酸三乙酯2 g,滑石粉5 g,95%乙醇200 mL。包衣片在人工胃液中2小时内无药物释放,在人工小肠液中4小时内无药物释放,在人工结肠液中大量释放,8小时内药物累积释药百分率达到标示量的90%以上,达到结肠定位制剂释药要求。结论:该方法稳定可行,可用于葛根芩连结肠定位片的成型工艺研究。Objective: To optimize the preparation technology of Gegen Qinlian colon positioning tablets. Methods: According to the pH and time dependent double drug release principle, the optimal compression and coating technology of Gegen Qinlian colon positioning coating tablets were optimized, and the positioning core was prepared by direct powder compression method, and the Gegen Qinlian colon positioning tablets were prepared by multilayer film coating. Single factor method was used to investigate the influencing factors of coating prescription, and Box-Behnken response surface method was used to further optimize the prescription to screen out the best prescription range. According to the optimized formulation and preparation technology, colon positioning tablets and ordinary tablets were prepared and the release degree of in vitro experiment was conducted. Results: The tablet core formulation consisted of 40% extractum powder, 26.75% microcrystalline cellulose, 26.75% lactose, 6% sodium carboxymethyl starch and 0.5% magnesium stearate. The coating prescription was coated with delay layer and enteric layer from inside to outside, the coating weight gain was 1.0% and 4.44%, respectively. The coating prescription was Eudragit RL:RS (1:2) 10 g, diethyl phthalate 1 g, talc powder 5 g, 95% ethanol 200 mL. The enteric layer prescription was Eudragit L:S (1:5) 10 g, triethyl citrate 2 g, talc powder 5 g, 95% ethanol 200 mL. There was no drug release in the artificial gastric juice within 2 hours, no drug release in the artificial small intestine fluid within 4 hours, and a large amount of drug release in the artificial colon fluid, and the cumulative drug release percentage reached more than 90% of the labeled amount within 8 hours, to meet the requirements of colonic localization drug release. Conclusion: The method is stable and feasible, and can be used to study the molding process of Gegen Qinlian colon positioning tablets.