Enhancement of dissolution rate and oral bioavailability in beagle dogs of oleanolic acid by adsorbing onto porous silica using supercritical carbon dioxide

• Published in: Journal of drug delivery science and technology Vol. 24; no. 4; pp. 380 - 385
• Main Authors: Li, Yuanyuan, Liu, Hongzhuo, Guo, Bei, Li, Yun, Geng, Yajie, Zhao, Furong, Zhang, Tianhong
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2014
• Subjects: Bioavailability; Dissolution; Fumed silica; Oleanolic acid; Supercritical carbon dioxide; Supercritical carbon dioxide; Bioavailability; Dissolution; Fumed silica; Oleanolic acid
• ISSN: 1773-2247
• DOI: 10.1016/S1773-2247(14)50077-9

The purpose of this study was to improve the dissolution rate and oral bioavailability of a poorly water-soluble herbal active component named oleanolic acid (OA) in beagle dogs. OA was adsorbed onto fumed silica via supercritical carbon dioxide (scCO2) and the physicochemistry properties of OA-silica powder were evaluated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), fourier transformed infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In the dissolution test, the optimal OA-silica solid dispersions showed a significant enhanced dissolution rate compared with commercial tablets and physical mixtures. While the results of bioavailability study in beagle dogs indicatated that OA-silica solid dispersions exhibited higher AUC and Cmax than commercial tablets (p < 0.05), with a 1.9-fold higher improvement in bioavailability for the absorption of OA from solid dispersions The enhanced dissolution and oral bioavailability of OA-silica solid dispersions were primarily attributed to the amorphous state and good dispersion of OA. The present investigation illustrated the feasibility of applying scCO2 to prepare solid dispersions, and employing them to improve the dissolution and oral bioavailability for poorly water-soluble pharmaceuticals such as OA.