Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid

作者：Gao, Nannan; Guo, Mengran; Fu, Qiang^*; He, Zhonggui^*

来源：Asian Journal of Pharmaceutical Sciences, 2017, 12(1): 66-72.

DOI：10.1016/j.ajps.2016.06.006

• Hot melt extrusion
• Solid dispersion
• Oleanolic acid
• Dissolution rate
• Oral bioavailability

The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid (OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion (HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test. The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64 (OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture (PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC (P < 0.05) and C-max (P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.

• 出版日期2017-1
• 单位沈阳药科大学