两亲性PCL-PVP聚合物水凝胶负载布洛芬-精氨酸药物共晶制备及体外释放研究

Preparation and in vitro release of ibuprofen-arginine pharmaceutical cocrystal loaded amphiphilic PCL-PVP polymer hydrogel

目的:制备两亲性聚己内酯-聚乙烯吡咯烷酮(PCL-PVP)聚合物水凝胶用于负载布洛芬-精氨酸药物共晶并考察其体外释放行为。方法:采用溶剂挥发法制备物质的量比1∶1布洛芬-精氨酸药物共晶;通过自由基溶液聚合法制备PCL-PVP聚合物凝胶。将布洛芬-精氨酸共晶负载于PCL-PVP聚合物凝胶上,考察不同亲疏水比例载药物共晶凝胶(PCL∶PVP=1∶9,3∶7,5∶5)在pH 5.8,7.4的PBS中的体外释放行为。结果:在pH 5.8 PBS中,布洛芬释放速率及释放量受载药凝胶亲疏水比例影响较大,释放72 h后, PCL∶PVP=3∶7的载药凝胶累积释放量达到约80%,为3组凝胶中的最大值。在pH 7.4 PBS中,不同亲疏水比例的载药凝胶的释放速率差别不大,布洛芬的释放速率较pH 5.8 PBS中的释放速率明显增大,在释放开始12 h后三者累积释放率均已接近或超过80%。结论:药物共晶的体外释放受多种因素影响,两亲性PCL-PVP聚合物凝胶可用于布洛芬-精氨酸药物共晶的载体,具有一定控释作用。

OBJECTIVE To prepare amphiphilic polycaprolactone-polyvinylpyrrolidone(PCL-PVP)polymer hydrogel for loading ibuprofen-arginine pharmaceutical cocrystal and investigate its release behavior in vitro.METHODS 1∶1 molar ratio cocrystal of ibuprofen-arginine was prepared through solution evaporation method.PCL-PVP polymer hydrogel was prepared through free radical polymerization of N-vinyl pyrrolidone in ethyl acetate.Ibuprofen-arginine cocrystals were loaded onto PCL-PVP polymer gels to investigate the in vitro release behavior of drug-loaded cocrystals with different hydrophilic ratios(PCL∶PVP=1∶9,3∶7,5∶5)in PBS at pH 5.8 and 7.4.RESULTS In pH 5.8 PBS,the dissolution rate and release percent of ibuprofen was greatly affected by the ratio of PCL/PVP.Among the three PCL/PVP ratios,the 3∶7 PCL-PVP hydrogel show the largest release percent which was near to 80%after 72 h.In pH 7.4 PBS,there is no significant difference on release behavior between three drug loaded hydrogels.The release and dissolution rate of drug loaded hydrogels in pH 7.4 PBS is obviously higher than that in pH 5.8 PBS,and the release percent was near to or over 80%after only about 12 h of release.CONCLUSION The in vitro release of ibuprofen cocrystal was affected by several factors.The amphiphilic PCL-PVP hydrogel can be used as a good vector of ibuprofen-arginine drug cocrystal delivery with controlled release.