Chameleonic Effect of Sulfanilamide and Sulfamethazine in Solvent Mixtures. Solubility Curves with Two Maxima.

Abstract

A quantitative approach is used in this work to reproduce the solubility profile of drugs in solvent mixtures showing two solubility maxima. The solubilities of sulfanilamide and sulfamethazine were determined at 25°C in two mixtures of varying polarity (ethyl acetate-ethanol and ethanol-water). A plot of the mole fraction of the drugs versus the solubility parameter of the solvent mixtures shows two solubility peaks. This unusual behavior cannot be described using the Extended Hildebrand method; it is probably a result of the chameleonic effect first described by Hoy. An equation including solute-solvent interaction terms represented by the acidec and basic partial solubility parameters, together with the Hildebrand solubility parameters of the solvent mixtures, is used to reproduce the experimental solubilities. The equation yields the two solubility maxima as found experimentally.Furthermore, the solubilities of sulfanilamide and sulfamethazine in two solvent mixtures are combined into a single equation to reproduce the two solubility maxima found for each drug. The equation is also able to predict the solubility curve of sulfamethoxypyridazine. The results show that the chameleonic effect can be described in a quantitative way in terms of Lewis acid-base interactions as represented by acidic and basic solubility parameters. Hildebrand solubility parameters, as well as the acidic and basic solubility parameters, are tabulated and they can be calculated for solvent mixtures, making easier the prediction of the best solvent mixture for a drug.