Abstract Sorafenib tosylate (SFNt) is an important numerouskinase inhibitor for the curement of cancers. It is commercially available (Nexavar) in the form of SFNt due to its poor aqueous solubility. Studies have been done to further enhance the dissolution property of the form SFNt, which could ultimately reasonable the currently high daily dose and frequency. In the present investigation, SFNt solid dispersions (SFNt-SD) were prepared through methods that combined two industrially well-accepted techniques of physical, melting and solvent evaporation. SFNt was co-mixed, melted and evaporated with hydrophilic polymers (Poloxamer 188). The process enabled the formation of SFNt-SD without using any toxic organic solvents, and the drug/carrier ratio (1:1, 1:3, and 1:5). The solid dispersion was characterised in terms of Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD). The FTIR spectra revealed the drug was found compatible and did not show any interaction with polymer, PXRD spectra showed clear transformation of crystalline to an amorphous form of drug particles. In-vitro dissolution study was performed in dissolution medium i.e. 0.1N HCL (pH 1.2). Cumulative percent drug release from SDs prepared by SE method was faster than from the pure drug, physical mixture (PM) and SDs prepared by MM method. The maximum percent drug release (93.43 ± 0.57) was found with PL 188 in the ratio of 1:5 (w/w). The solubility of drug was increased in concentration dependent manner of polymer and follow linearity order. The enhanced dissolution behaviour of SFNt-NP was possible with an optimized technique of solid dispersions. Solvent evaporation was able to increase the surface area with reduced crystallite size, which accelerated the dissolution of SFNt-SD. This method and drug/carrier combination ratio could be easily extended to other low water soluble active pharmaceutical drug candidates as a handing approach to enhance their solubility and dissolution properties.
Keywords Solubility enhancement, Solid dispersion, Solvent evaporation, Sorafenib tosylate (SFNt), Anticancer.