Preparation and characterization of solid dispersion using a novel amphiphilic copolymer to enhance dissolution and oral bioavailability of sorafenib

초록

The objective of the current study was to enhance dissolution and oral bioavailability of the poorly water-soluble drug, sorafenib (SFN), by solid dispersion (SD) technique using a novel amphiphilic copolymer, polyvinyl caprolactam-polyvinyl acetate-polyethyleneglycol graft copolymer (Soluplus). The SD formulations were prepared by the spray drying method with SFN, Soluplus, and sodium lauryl sulfate (SLS) at various weight ratios in water. The optimized SD formulation, which showed the highest dissolution rate in distilled water, was further characterized for surface morphology, crystallinity, dissolution in pH 1.2, pH 4.0, and pH 6.8, and pharmacokinetics in rats. Powder X-ray diffraction and differential scanning calorimetry revealed the amorphous form of SFN in the formulation. In addition, at the oral dosage of 20 mg/kg SFN, the SD formulation showed increased C-max and AUC(0-48h) by 1.5- and 1.8-fold, compared to those of SFN powder, respectively (p < 0.05). These findings suggest that the preparation of SFN-loaded SD using Soluplus could be a promising strategy for improvement of oral bioavailability of SFN. (C) 2015 Elsevier B.V. All rights reserved.

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