黄芩素-茶碱共晶的溶剂体系筛选及体外溶出度评价

Solvent optimization and in vitro dissolution evaluation of baicalein-theophylline cocrystal

关键词:  黄芩素  茶碱  共晶  三元相图  溶出度

Key words:  baicalein  theophylline  cocrystal  ternary phase diagram  dissolution rate

摘要:

[目的] 优选制备黄芩素-茶碱共晶的溶剂体系，通过体外溶出实验考察共晶对黄芩素和茶碱各自溶出度的影响。[方法] 通过测定黄芩素-茶碱共晶在茶碱-乙酸乙酯、茶碱-甲醇和茶碱-丙酮溶液中的溶解度，得出三相平衡点，绘制黄芩素-茶碱-溶剂体系的三元相图，筛选最优溶剂体系制备共晶，并以人工肠液和人工胃液为溶出介质，对共晶进行体外溶出度评价。[结果] 丙酮溶液体系中的共晶形成区面积大于乙酸乙酯、甲醇。通过丙酮溶剂挥发法制备的共晶中，黄芩素在人工肠液和人工胃液中的累积溶出度分别是原料药的1.38和2.02倍，分别是物理混合物的1.27和1.80倍。两种介质中共晶对茶碱均起到了一定的缓释作用。[结论] 共晶的形成能够促进难溶性成分黄芩素的体外溶出度，并且对茶碱的溶出度有一定延缓作用，为黄芩素-茶碱共晶的进一步研究和临床应用提供了借鉴。

Abstract:

[Objective] To optimize the solvent in the preparation of baicalein-theophylline cocrystal and investigate its dissolution behavior in vitro.[Methods] By determining the solubility of baicalein-theophylline cocrystal in theophylline-ethyl acetate,theophylline-methanol and theophylline-acetone solutions,the ternary phase diagram of the baicalein-theophylline-solvent system was drawn to screen the solvent in preparation process. The in vitro dissolution rate of the cocrystal was evaluated by using the simulated intestinal fluid (SIF) and the simulated gastric fluid (SGF) as the dissolution medium.[Results] The area of cocrystal conformation in acetone solution system was larger than that of ethyl acetate and methanol. Thus,baicalein-theophylline cocrystal was obtained by acetone co-solvent method. The dissolution rate of baicalein in SIF and SGF was 1.38 fold and 2.02 fold than that of raw material,and was 1.27 fold and 1.80 fold than that of physical mixture,respectively. The cocrystal in both media has a certain sustained release effect on theophylline.[Conclusion] The formation of cocrystal could promote the in vitro dissolution rate of the poorly soluble component baicalein,and also reduce the dissolution rate of theophylline,which provides evidences for further research and clinical application of baicalein-theophylline cocrystal.