Solubility and limiting activity coefficient of simvastatin in different organic solvents

Equilibrium mole fraction solubility of Zocor® (simvastatin) a pharmaceutically important compound, was measured between 279 and 315 K, in fifteen different industrial-relevant organic solvents including: methyl acetate, ethyl acetate, propyl acetate, iso-propyl acetate, butyl acetate, iso-butyl acetate, sec-butyl acetate, tert-butyl acetate, and ethanol, propanol, 1-butanol, 2-butanol, 1-pentanol, 1-hexanol, and 1-octanol. Fusion enthalpy, ΔfusH, melting point temperature, Tm, were measured to be 32,169 J/mol, 412.6 K, respectively; and the difference in the molar heat capacity (at constant pressure) of the liquid, and solid form of simvastatin, ΔCP, was approximated (by extrapolation) to be 230 J/mol K. Dissolution of simvastatin was found to be endothermic, and entropically favorable. The activity coefficient at infinite dilution of simvastatin in each solvent was calculated from the experimental data, then fitted to Gibbs–Helmholtz equation to estimate the limiting partial molar excess enthalpies, H¯E,∞, and the limiting partial molar excess entropies, S¯E,∞. The data was also fitted to the non-random-two-liquid (NRTL) activity coefficient equation to generate the model interaction parameters for dissolution of simvastatin in the organic solvents studied here.