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

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 (<i>c_p</i>) occuring upon formation of a binary drug-polymer solid dispersion. Thermodynamic model accounting for those <i>c_p</i> changes is used to estimate the Gibbs free energy of mixing (<i>G</i>^M) and thus the equilibrium solubility of LRS HCl in PVP solid dispersions.