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.
Ren
Ke
K
Key Laboratory of Drug Targeting, West China School of Pharmacy, Sichuan University. Chengdu, PR China.
Zhang
Zhirong
Z
Li
Yanzhen
Y
Liu
Jie
J
Zhao
Dong
D
Zhao
Yi
Y
Gong
Tao
T
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000737:chemistry* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005260:Female; D007700:Kinetics; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012995:Solubility; D012997:Solvents; D013816:Thermodynamics; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004337:Drug Carriers; D012997:Solvents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C030419:andrographolide