Solubility and Pseudopolymorphic Transitions in Mixed Solvents: Sodium Naproxen in Methanol-Water and Ethanol-Water Solutions

The solubility of sodium naproxen in methanol water and ethanol water solutions was determined as functions of temperature and solvent composition over a temperature range of 10-40 degrees C and the entire range of alcohol water compositions. Data were correlated using an expression in the form of the van't Hoff equation, which allowed estimation of heats and entropies of dissolution. In addition, the correlations indicated that different forms (hydrates and alcohol solvates) existed in different regions of the temperature solvent composition space. Thermal analysis and powder X-ray diffraction of samples of the equilibrated solids confirmed the existence of the different pseudopolymorphic forms. Conditions at which the more stable form of the sodium naproxen became the less stable form were determined and are referred to as transition points; at such conditions, the solution and two solid forms were in equilibrium. The activity of water at the transition points was estimated from the Wilson equations and found to be the same irrespective of the alcohol present in the system.