普拉格雷/β-环糊精包合物的制备工艺研究

Study on the Preparation Technology of Prasugrel/β-cyclodextrin Inclusion Compound

目的:筛选普拉格雷/β-环糊精包合物的制备工艺,提高该药口服制剂的生物利用度。方法:以普拉格雷为原料、β-环糊精为辅料,分别采用溶液法和研磨法制备不同物料质量比(溶液法为1∶1、1∶3、1∶5、研磨法为1∶1、1∶2、1∶3、1∶5)的普拉格雷/β-环糊精包合物,测定其包封率和载药量。分别以p H 4.5醋酸盐缓冲液或p H 6.8磷酸盐缓冲液为溶出介质,检测其30 min内的体外溶出度。结果:溶液法制备的包合物包封率依次为27.42%、81.85%、83.51%,载药量依次为19.61%、73.24%、75.35%,在醋酸盐缓冲液中30 min的溶出度分别为41.18%、68.67%、61.32%,在磷酸盐缓冲液中30 min的溶出度分别为4.2%、17.20%、16.59%;研磨法制备的包合物包封率依次为20.13%、58.69%、65.18%、79.36%,载药量依次为12.64%、47.32%、52.16%、70.52%,在醋酸盐缓冲液中30 min的溶出度分别为36.71%、52.08%、53.06%、54.34%,在磷酸盐缓冲液中30 min的溶出度分别为5.72%、9.04%、10.46%、21.79%。盐酸普拉格雷原料药在醋酸盐缓冲液中30 min的溶出度为43.42%,在磷酸盐缓冲液中30 min的溶出度为6.94%。结论:以普拉格雷/β-环糊精投料质量比为1∶3、采用溶液法制备包合物略优。

OBJECTIVE： To screen the preparation technology of Prasugrel/β-cyclodextrin inclusion compound, and to provide bioavailability of it. METHODS： Using prasugrel as raw material and β-cyclodextrin as excipients, the solution method and grind- ing method were used to prepare Prasugrel/β-cyclodextrin inclusion compound with different material ratios （solution method： 1 ： 1, 1 ： 3, 1 ： 5; grinding method： 1 ： 1, 1 ： 2, 1 ： 3, 1 ： 5）. The entrapment efficiency and drug-loading rate of the inclusion compound were also determined. Using acetate buffer solution with pH 4.5 and phosphate buffer solution with pH 6.8 as dissolution medium, the dissolution rate of the inclusion compound were determined within 30 min. RESULTS： The entrapment efficiencies of the inclu- sion compound prepared by dissolution method were 27.42%, 81.85% and 83.51%, and the drug-loading rate of it were 19.61%, 73.24% and 75.35%, respectively; the dissolution rates of it in acetate buffer solution were 41.18%, 68.67% and 61.32% within 30 min, and those of it in phosphate buffer solution were 4.2%, 17.20% and 16.59% within 30 min. The entrapment efficiencies of the inclusion compound prepared by grinding method were 20.13%, 58.69%, 65.18% and 79.36%, and the drug-loading rate of it were 12.64%, 47.32%, 52.16% and 70.52%, respectively; the dissolution rates of it in acetate buffer solution were 36.71%, 52.08%, 53.06% and 54.34% within 30 min, and those of it in phosphate buffer solution were 5.72%, 9.04%, 10.46%, 21.79% within 30 min. The dissolution rate of prasugrel hydrochloride raw material in acetate buffer solution was 43.42% and in phosphate buffer solution was 6.94% within 30 rain. CONCLUSIONS： The compound prepared by solution method with the ratio of prasugrel to β-cyclodextrin 1 ： 3 is better.