熊果酸共晶固体分散体的体外特性研究

In vitro characteristic evaluation of ursolic acid co-crystal solid dispersions

目的采用共晶与固体分散体技术相结合策略,筛选合适的载体材料制备熊果酸共晶的固体分散体,更进一步提高熊果酸的溶解度、溶出度,以更好地改善其生物利用度。方法选择泊洛沙姆188(F68)、聚维酮S630(PVP-S630)、硬脂酸聚烃氧(40)(S40)和羟丙甲纤维素(HPMC)4种载体材料,采用溶剂法,分别将原药、熊果酸-哌嗪共晶(UA-PP)与不同载体制成固体分散体。测定溶解度,进行体外溶出实验,比较并评价熊果酸制成共晶和固体分散体后改善生物利用度的潜力。结果熊果酸共晶和熊果酸固体分散体均能增加熊果酸的溶解度和溶出度。共晶制成固体分散体后能进一步提高熊果酸的溶解度,加快其体外溶出。结论将熊果酸共晶制成固体分散体后其溶解度和溶出度显著优于熊果酸共晶和熊果酸固体分散体。

Objective To use co-crystal and solid dispersion technology, screen a suitable carrier material to prepare ursolic acid （UA） co-crystal solid dispersion in order to improve the solubility and dissolution of UA. Methods UA and UA piperazine co-crystal （UA-PP） solid dispersions were prepared with solvent method by using four carriers, respectively. The solubility and in vitro dissolution of free drug, co-crystal, and solid dispersions were determined. Results The solubility of UA and UA-PP solid dispersions was significantly higher than free drug and its physical mixtures. Solid dispersion technology could further increase the solubility of UA-PP and accelerate its in vitro dissolution rate. The result layed the foundation for the development of a novel oral formulation of ursolic acid. Conclusion The co-crystal and solid dispersion technology could improve the solubility and dissolution of UA. The UA-PP solid dispersions show the best improvement in the solubility and dissolution of UA.