Solvent and temperature effects on the solubility of some new adamantane/memantine sulfonamide derivatives

Abstract

The dissolution processes of five new adamantane/memantine sulfonamide derivatives with different substituents in the phenyl ring were examined in the pharmaceutically relevant solvents: aqueous buffer pH 7.4, 1-octanol and n-hexane by the shake-flask method in the temperature range of 293.15–313.15 K. Compounds revealed low equilibrium solubility in water and n-hexane, and essentially better solubility in 1-octanol. Experimental solubility was correlated with the melting properties (measure of crystal lattice energy) and hypothetic distribution coefficient (measure of solvation). Neuroprotective potential of the investigated derivatives was accessed with the help of ΔlogD parameter. The solubility evaluation using the Hansen solubility parameters showed the consistency with the experimental data and revealed the trends in the structure modification within the studied class in order to achieve good potential adsorption. The activity coefficients at infinite dilution, ideal solubility of the compounds in the solvents and molar excess thermodynamic functions have been calculated. Ideal solubility was recorded much higher than the experimental one at each temperature. It has been estimated that in most cases the entropy term of the excess Gibbs energy is responsible for the deviation from ideality in the investigated drug-solvent systems. The solubility data and thermodynamic properties obtained would be useful in the process of purification, recrystallization and dosage form design of adamantane/memantine sulfonamide derivatives in pharmaceutical industry.