目的 采用共晶與固體分散體技術(shù)相結(jié)合策略，篩選合適的載體材料制備熊果酸共晶的固體分散體，更進(jìn)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 選擇泊洛沙姆188（F68）、聚維酮S630（PVP-S630）、硬脂酸聚烴氧（40）（S40）和羥丙甲纖維素（HPMC）4種載體材料，采用溶劑法，分別將原藥、熊果酸-哌嗪共晶（UA-PP）與不同載體制成固體分散體。測定溶解度，進(jìn)行體外溶出實(shí)驗(yàn)，比較并評(píng)價(jià)熊果酸制成共晶和固體分散體后改善生物利用度的潛力。結(jié)果 熊果酸共晶和熊果酸固體分散體均能增加熊果酸的溶解度和溶出度。共晶制成固體分散體后能進(jìn)一步提高熊果酸的溶解度，加快其體外溶出。結(jié)論 將熊果酸共晶制成固體分散體后其溶解度和溶出度顯著優(yōu)于熊果酸共晶和熊果酸固體分散體。

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.

上海市科委中藥現(xiàn)代化專項(xiàng)（10DZ1972600）