Thermodynamic modeling of pharmaceutical substance solubility: A review of various models

Crystallization and extraction are the most significant methods for purifying the industrialand biological substances as constituent of chemical and pharmaceutical products. The designand control of these mentioned methods need the solute solubility data which change based ontemperature and solvent composition. Therefore, an accurate solubility data measurement whichfrequently involves the various solvents solubility evaluation at several temperatures, is soessential for designing and scaling up the crystallization process, and is indispensable for gettingknowledge of phase equilibria. One of the preliminary endeavors for giving a distinguishedinformation of pharmaceutical processes is modeling and presenting a relatively simplemathematical model to predict the solubility of various drugs. The essence of ongoing paper isrelated to solubility prediction in pharmaceutical substances with different chemical structuresapplying different thermodynamic models involving various parameters in a wide range oftemperatures. The NRTL model, UNIQUAC model, Wilson model, Modified Apelblat model,Scatchard-Hildebrand model, and Extended Pitzer model are so illustrative among the presentedmodels which are utilized in drugs calculations. For instance, Chao Cheng et al. [1] measured thesolubility of 4-nitrobenzaldehyde in different solvents including methanol, isopropanol, acetone,ethanol, and toluene using the atmospheric saturation method under atmospheric pressure anddifferent temperatures. They also applied the NRTL model, Apelblat model, and Wilson modelto predict the solubility and other desired parameters. This team concentrated on solubilityprediction of the dehydroepiandrosterone acetate in different solvents containing cyclohexane,acetonitrile, methanol, etc using modified Apelblat equation, the λh equation, the Wilson model,and the NRTL model [2]. Reviewing the papers shows that using the conventionalthermodynamic models, and predicting the solubility of drug in different single and mixedsolvents have an error about 30%. Obviously, the new thermodynamic models with less errorsshould be introduced. Definitely, the molecular structure of drugs affects their solubility, and itshould be offered a model that shows the structural properties of the substance.

کلیدواژه ها:

Thermodynamic Modeling ، Solubility Equilibrium ، GE Models ، Co-Solvents ، Pharmaceutical Substances