Physicochemical characteristics and oral bioavailability of andrographolide complexed with hydroxypropyl-beta-cyclodextrin.
Physicochemical characteristics and oral bioavailability of andrographolide complexed with hydroxypropyl-beta-cyclodextrin.
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发表时间：
2009-08
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通讯作者：
Ke Ren;Zhirong Zhang;Yanzhen Li;Jie Liu;Dong Zhao;Yi Zhao;T. Gong
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作者：
Ke Ren;Zhirong Zhang;Yanzhen Li;Jie Liu;Dong Zhao;Yi Zhao;T. Gong
采用羟丙基-β-环糊精（HP-β-CD）包合穿心莲内酯（AND），可显著提高其溶解度。采用溶剂挥发法制备了包合物，并用相溶解度法、X射线衍射法和差示扫描量热法对包合物进行了表征。AND的溶解度随HP-β-CD浓度的增加而线性增加，形成A（L）型相溶解度图。分子模拟计算用于预测HP-β-CD空腔内AND的可能取向。体外溶出曲线显示，与未包合的药物相比，包合物的溶出速率和百分比显著增加。体内药代动力学研究表明，口服给药后，AUC（0-无穷大）是AND混悬液的1.6倍。这些结果表明，HP-β-CD包合系统可能是一种有前途的口服给药制剂。
A significant increase in solubility of andrographolide (AND), a slightly water soluble anti-inflammatory and antimicrobial drug, was achieved by inclusion with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The inclusion complex was prepared by solvent evaporation and characterized by the phase solubility method, X-ray diffractometry and differential scanning calorimetry. The solubility of AND increased linearly as a function of HP-beta-CD concentration, resulting in A(L)-type phase solubility diagram. Molecular modeling calculations were used to foresee the possible orientations of AND inside the HP-beta-CD cavity. The in vitro dissolution profile showed a significant increase in dissolving rate and percent of the inclusion complex compared with uncomplexed drug. In vivo pharmacokinetic study showed that AUC(0-infinity) was 1.6-fold higher than that of AND suspension after oral administration. These results suggest that HP-beta-CD inclusion system might be a promising formulation for the oral delivery of AND.