Prediction of solubility curves and melting properties of organic and pharmaceutical compounds.
The relationships between solubility, temperature dependence of solubility, melting temperature and melting enthalpy are investigated for the purpose of finding relations that can significantly reduce the need for experimental work in the selection of the solvent for processing of organic fine chemicals and pharmaceuticals. The relationships are investigated theoretically and by evaluation of experimental data for 41 organic and pharmaceutical compounds comprising a total of 115 solubility curves in organic and aqueous solvents. The work considers (i) selection of the equation for correlation of solubility data based on thermodynamic considerations and ability to predict melting properties of the solute from solubility data, (ii) prediction of the temperature dependence of solubility, and (iii) prediction of solubility curves in new solvents. While it is a simple task to find an equation to obtain a decent fit of experimental solubility data, it is more challenging to find relations that are sufficiently sound thermodynamically to allow for extrapolation to the melting temperature. However, with a proper choice of equation it is shown that the melting temperature of the solute can readily be predicted from solubility data in organic solvents (average accuracy of -5K, standard deviation of 26K). Relationships are identified by which the entire solubility curve can be predicted of the compound in a new solvent using only the melting properties and a single solubility data point in that solvent.
Nordström
Fredrik L
FL
Department of Chemical Engineering and Technology, Royal Institute of Technology, SE-100 44 Stockholm, Sweden. fredrik.nordstrom@ket.kth.se
Rasmuson
Ake C
AC
D000465:Algorithms; D015233:Models, Statistical; D008962:Models, Theoretical; D009930:Organic Chemicals / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012044:Regression Analysis; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D044366:Transition Temperature
D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012997:Solvents