Solid-state properties of drugs. I. Estimation of heat capacities for fusion and thermodynamic functions for solution from aqueous solubility-temperature dependence measurements

Abstract

A novel equation was developed to describe solubility-temperature dependence data for some polar solids (acetaminophen, barbiturates and parabens) in water. Fitting of data to the equation by non-linear regression was tested with error-free model data similar to the experimental data. All coefficients for the equation were recovered from error-free data with an accuracy of ±0.04% at best and ±0.56% at worst. The fitting procedure for real data estimated apparent thermodynamic functions (enthalpy, entropy and heat capacity) for the solution process (using the hypothetical one mole fraction solution behaving at infinite dilution as the standard state) and also the heat capacity change for fusion of the solid drugs. The apparent thermodynamic functions for real data were estimated with good precision, based on tests. The estimated changes in heat capacity for fusion were similar in magnitude to those obtained by an independent method. The thermodynamic functions for solution and for fusion displayed trends with molecular structure in some cases.