Sorafenib tosylate incorporation into mesoporous starch xerogel for in-situ micronization and oral bioavailability enhancement

Abstract

Poorly water-soluble drugs like sorafenib tosylate (SFB) can be made more soluble and orally bioavailable using a biocompatible hydrophilic matrix yields amorphous or microcrystalline drugs with high stability and low recrystallization risk. Mesoporous starch (MPS) due to its edibility, biodegradability, high surface area, and confined pores. In this study, MPS, either alone or in combination with polyvinylpyrrolidone (PVP), was employed for improving SFB oral bioavailability. To this aim, MPS was prepared in three steps: gelatinization, solvent exchange, and vacuum drying, after which it was used to incorporate SFB at various ratios using the immersion/solvent evaporation technique. Nitrogen adsorption/desorption analysis, Fourier transform infrared spectrometry (FTIR), field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (XRD) crystallography, and differential scanning calorimetry (DSC) were used to characterize SFB-loaded and drug-free samples, which confirmed the successful preparation of mesoporous structures with desirable uniform porosity, small pore size (about 5.3 nm), and specific surface area of about 24 m²/g. In-vitro dissolution testing revealed that the SFB dissolution rate increased substantially for the loaded MPS or MPS-PVP samples. Furthermore, when SFB was loaded in MPS-PVP, single-dose pharmacokinetics in rats confirmed an enhanced oral absorption kinetic. Therefore, impregnation of poorly soluble drugs such as SFB in the PVP-modified MPS excipient, which is constructed from a combination of mesoporous materials and a drug recrystallization inhibitor such as hydrophilic polymers, is proposed as a promising strategy for desirable enhancements in drug solubility, oral bioavailability, and efficacy.

Keywords:

• Starch
• mesoporous
• sorafenib tosylate
• oral bioavailability
• pharmacokinetics

Acknowledgment

The authors acknowledge the support and use of facilities at the Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences.

Disclosure statement

No potential conflict of interest was reported by the author(s).