Characterization and In Vivo Evaluation of an Inclusion Complex of Oridonin and 2-hydroxypropyl-β-cyclodextrin

Abstract

Oridonin, a diterpenoid, is a sparingly soluble compound and its aqueous solubility can't meet the requirement of clinical intravenous administration. This study was, accordingly, to prepare an inclusion complex of oridonin and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by lyophilization to improve its apparent solubility. The solubility enhancement of oridonin was evaluated by phase solubility method, and the phase solubility curve displayed a typical A_L-type, indicating the formation of 1:1 inclusion complex. The formation of inclusion complex was confirmed by DSC, XRD, FTIR, and NMR, and thereby two possible inclusion modes were inferred. In vivo studies demonstrated that HP-β-CD had no significant effect on the plasma pharmacokinetic behaviors of oridonin following i.v. administration to rats, but the inclusion complex tended to decrease the distribution of oridonin in heart, spleen, and kidney and increase that in lung in mice, compared to that of free drug.

keywords:

• oridonin
• 2-hydroxypropyl-β-cyclodextrin
• inclusion complex
• characterization
• pharmacokinetics
• tissue distribution