Solubilization and formulation of chrysosplenol C in solid dispersion with hydrophilic carriers

Abstract

We investigated how to overcome problems associated with the solubility, dissolution, and oral bioavailability of the poorly water-soluble drug compound, chrysosplenol C (CRSP), as well as the effects of single and binary hydrophilic polymers (PVP K-25 and/or PEG 6000) on the solubility and dissolution parameters of CRSP. Then an optimized formulation was further developed with a surfactant. To select a surfactant suitable for a CRSP-loaded solid dispersion (SD), the solubility of CRSP in distilled water containing 1% surfactant was compared with the solubilities in other surfactants. Sodium lauryl sulfate (SLS) showed the highest drug solubility. Overall, a formulation containing CRSP, binary hydrophilic polymers (PVP and PEG 6000), and SLS at a ratio of 2.0/0.2/1.1/0.7 showed the optimum in vitro release profile. This optimized formulation had better safety properties than pure CRSP in cell viability examinations. SD formulations were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy. Our optimized SD formulation is expected to improve the bioavailability of CRPS because it improves the solubility and dissolution rate of CRSP. (C) 2016 Elsevier B.V. All rights reserved.