Thermodynamics of solutions I: benzoic acid and acetylsalicylic acid as models for drug substances and the prediction of solubility.
OBJECTIVE
To investigate the solution process of drug substances (exemplified by benzoic acid. BA. and acetylsalicylic acid, ASA), particularly the interrelation between enthalpic and entropic terms of Gibbs energy, in different solvents. To develop an approach for the estimation of standard solution enthalpies based on a self-consistent thermochemical scale.


METHODS
Two independent methods, solubility experiments (concentrations of saturated solutions) and solution calorimetry (standard solution enthalpies) in aliphatic alcohols and individual organic solvents were used. Correlation between the thermodynamic functions in various solvents were analyzed by standard statistical methods. Multiple regression analysis between delta Ho(sol) values and the parameters of the solvents was run on the Koppel-Palm equation.


RESULTS
Based on experimental data, a compensation effect between thermodynamic functions was observed. Correlation was found between delta Ho (sol) (BA) and delta Ho(sol) (ASA) [where the delta Ho(sol) (BA)-values were used as a self-consistent thermochemical scale]. Furthermore, delta Ho(sol) correlated with the Koppel-Palm basicity of the solvents.


CONCLUSIONS
The model based on solubility and solution experiments might be useful for the prediction of solubility or solvation of drug substances in different media. The regression equation based on the self-consistent thermochemical scale makes it possible to approximate the ability to solvate a drug substance in comparison with structure-relative substances.
Perlovichl
German L
GL
University of Tromsø, Institute of Pharmacy, Breivika, N-9037 Tromsø, Norway.
Bauer-Brandl
Annette
A
D000438:Alcohols / Q000737:chemistry; D001241:Aspirin / Q000737:chemistry*; D019817:Benzoic Acid / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008433:Mathematics; D008956:Models, Chemical; D012995:Solubility; D012997:Solvents; D013816:Thermodynamics
D000438:Alcohols; D012997:Solvents; D019817:Benzoic Acid; D001241:Aspirin