Enthalpy and entropy contributions to the solubility of sulphamethoxypyridazine in solvent mixtures showing two solubility maxima

J Pharm Pharmacol. 1995 Jul;47(7):550-5. doi: 10.1111/j.2042-7158.1995.tb06712.x.


The solubility of sulphamethoxypyridazine was measured at several temperatures in mixtures of water:ethanol and ethanol:ethyl acetate. Sulphamethoxypyridazine was chosen as a model drug to compare the solvation effects of proton donor-proton acceptor (water and ethanol) and proton acceptor (ethyl acetate) solvents and mixtures of these solvents because this drug contains functional groups capable of Lewis acid-base interaction. A plot of the mole fraction solubility against the solubility parameter (delta 1 = 30.87 MPa1/2 (20:80 v/v water:ethanol) and another at delta 1 = 20.88 MPa1/2 (30:70 v/v ethanol:ethyl acetate) at all the temperatures under study. The enthalpies and entropies of mixing as well as the enthalpies and entropies of transfer of sulphamethoxypyridazine from ethanol of mixing as well as the enthalpies and entropies of transfer of sulphamethoxypyridazine from ethanol to water:ethanol and ethanol:ethyl acetate mixtures were calculated to compare solvation characteristics of the solvent mixtures toward the drug. As ethanol is added to water, the entropy increases and the structure of the solvent mixture became less ordered, favouring the interaction of the drug with the solvent mixture. On the other hand, in the case of the ethanol:ethyl acetate mixture, solubility is favoured by the more negative enthalpy values. This way, the same result, i.e. a solubility maximum, is obtained by different routes. In the ethanol:water mixtures, the dissolution process if entropy-controlled while enthalpy is the driving force in the case of ethanol:ethyl acetate mixtures. The two solvent systems show enthalpy-entropy compensation. Water deviates from the linear relationship due possibly to its hydrophobic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Ethanol / chemistry
  • Hydrogen-Ion Concentration
  • Solubility
  • Sulfamethoxypyridazine / chemistry*
  • Technology, Pharmaceutical
  • Thermodynamics
  • Water / chemistry


  • Acetates
  • Water
  • Ethanol
  • ethyl acetate
  • Sulfamethoxypyridazine