Enhanced solubility and bioavailability of poorly water-soluble SM-458, a new synthetic drug using various solubilization techniques

Abstract

The aim of this research was to enhance the solubility and oral bioavailability of poorly water-soluble SM-458, a new synthetic drug using two-types of SM-458-loaded solid dispersion systems, such as solvent-evaporated and surface-attached solid dispersion. The effect of polymers and surfactants on the aqueous solubility of SM-458 was investigated, leading to selecting polyvinylpyrrolidone (PVP) and sodium lauryl sulphate (SLS). Employing spray-drying technique, numerous solvent-evaporated and surface-attached solid dispersion were prepared with various amounts PVP and SLS using ethanol and water, respectively. Their physicochemical properties, solubility, dissolution and oral bioavailability in rats were assessed compared to the drug powder. In this study, PVP hardly affected the drug solubility and dissolution, but SLS greatly did. Among solvent-evaporated solid dispersion systems tested, the solid dispersion composed of SM-458, PVP and SLS at the weight ratio of 1:5:1, provided highest drug solubility and dissolution. This solvent-evaporated solid dispersion gave the homogeneous and very small spherical particles, in which drug was changed to the amorphous state. Additionally, a surface-attached solid dispersion was prepared with the same compositions, as given above. In the surface-attached solid dispersion, the carriers were adhered onto the surface of the unchanged crystalline drug. The solubility, dissolution and oral bioavailability was significantly increased in the order of solvent-evaporated > surface-attached > drug powder. Thus, the types of solid dispersions considerably affected the physicochemical properties, aqueous solubility and oral bioavailability. Furthermore, the SM-458-loaded solvent-evaporated solid dispersion with highest oral bioavailability would be actively recommended as a practical oral pharmaceutical product.