Estimation of lurasidone hydrochloride equilibrium solubility in a polymeric solid dispersion using thermal analysis and thermodynamic modeling

Abstract

Information on drug equilibrium solubility is crucial in producing a stable drug product, prolonging its shelf-life and maintaining its reported properties. Such data regarding the antipsychotic drug lurasidone hydrochloride (LRS HCl), were non-existent up to this date. We have presented results that could facilitate the formation of stable LRS HCl solid dispersions using amorphous poly(vinyl-pyrrolidone) (PVP) as a carrier. For the purpose of drug solubility enhancement, solid dispersions with different drug loads were prepared by solvent evaporation method and characterized by thermogravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy (FT-IR). Thermal analysis has been used to detect the changes in heat capacity (cp ) occuring upon formation of a binary drug-polymer solid dispersion. Thermodynamic model accounting for those cp changes is used to estimate the Gibbs free energy of mixing (G M) and thus the equilibrium solubility of LRS HCl in PVP solid dispersions.