Improvement in solubility and bioavailability of puerarin by mechanochemical preparation

Abstract

An efficient and solvent-free procedure was developed to improve the solubility and bioavailability of the poorly water-soluble drug puerarin by mechanochemical technology. The stable inclusion complex of puerarin and 2-hydroxypropyl-β-cyclodextrin (HPCD) was prepared by a ball mill under the following conditions: equimolar ratio of puerarin to HPCD; rotational speed of 250 rpm; milling time of 90 min; steel balls of 22 mm diameter. The solid complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD), and fourier transformation-infrared spectroscopy (FT-IR). Mechanochemical action could result in enhanced molecular encapsulation, homogeneous distribution and amorphization of the drug. In comparison to puerarin, a 1.64-fold increase in absolute bioavailability was obtained. The solubility of the inclusion complex was 25.33-fold higher and the drug release amount reached 79.44% at 15 min, 2.76-fold higher.

Keywords::

• Mechanochemistry
• puerarin
• 2-hydroxypropyl-β-cyclodextrin
• physicochemical properties
• inclusion complex
• pharmacokinetics