CHAMELEONIC EFFECT OF SULFANILAMIDE AND SULFAMETHAZINE IN SOLVENT MIXTURES - SOLUBILITY CURVES WITH 2 MAXIMA

A quantitative approach is used in this work to reproduce the solubili ty profile of drugs in solvent mixtures showing two solubility maxima. The solubilities of sulfanilamide and sulfamethazine were determined at 25 degrees C in two mixtures of varying polarity (ethyl acetate-eth anol and ethanol-water). A plot of the mole fraction of the drugs vers us the solubility parameter of the solvent mixtures shows two solubili ty 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 interacti on terms represented by the acidic and basic partial solubility parame ters, together with the Hildebrand solubility parameters of the solven t mixtures, is used to reproduce the experimental solubilities. The eq uation yields the two solubility maxima as found experimentally. Furth ermore, the solubilities of sulfanilamide and sulfamethazine in two so lvent mixtures are combined into a single equation to reproduce the tw o solubility maxima found for each drug. The equation is also able to predict the solubility curve of sulfamethoxypyridazine. The results sh ow 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.