ENTHALPY AND ENTROPY CONTRIBUTIONS TO THE SOLUBILITY OF SULPHAMETHOXYPYRIDAZINE IN SOLVENT MIXTURES SHOWING 2 SOLUBILITY MAXIMA

The solubility of sulphamethoxypyridazine was measured at several temp eratures in mixtures of water:ethanol and ethanol:ethyl acetate. Sulph amethoxypyridazine was chosen as a model drug to compare the solvation effects of proton donor-proton acceptor (water and ethanol) and proto n acceptor (ethyl acetate) solvents and mixtures of these solvents bec ause this drug contains functional groups capable of Lewis acid-base i nteraction. A plot of the mole fraction solubility against the solubil ity parameter (delta(1)) of these solvent mixtures showed two solubili ty maxima, one at delta(1) = 30.87 MPa(1/2) (20:80 v/v water:ethanol) and another at delta(1) = 20.88 MPa(1/2) (30:70 v/v ethanol:ethyl acet ate) at all the temperatures under study, The enthalpies and entropies of mixing as well as the enthalpies and entropies of transfer of sulp hamethoxypyridazine from ethanol to water:ethanol and ethanol:ethyl ac etate mixtures were calculated to compare solvation characteristics of the solvent mixtures toward the drug. As ethanol is added to water, t he entropy increases and the structure of the solvent mixture became l ess ordered, favouring the interaction of the drug with the solvent mi xture. On the other hand, in the case of the ethanol:ethyl acetate mix ture, solubility is favoured by the more negative enthalpy values. Thi s way, the same result, i.e, a solubility maximum, is obtained by diff erent routes. In the ethanol:water mixtures, the dissolution process i s entropy-controlled while enthalpy is the driving force in the case o f ethanol:ethyl acetate mixtures. The two solvent systems show enthalp y-entropy compensation. Water deviates from the linear relationship du e possibly to its hydrophobic effect.