Physicochemical characteristics and oral bioavailability of andrographolide complexed with hydroxypropyl-beta-cyclodextrin.

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.