Application of Thermodynamic Models to Predict the Solubility of Biologically Active Substances

Abstract

Introduction. The choice of solvents for the processes of extraction of biologically active substances from natural raw materials, the processes of purification of natural and synthesized substances by extraction, crystallization and dissolution methods is an important problem of the modern pharmaceutical industry, because a large number of experiments must be performed to determine the optimal solvent or mixture of solvents. To reduce the cost of developing and optimizing the extraction and purification of substances stages, it is proposed to use thermodynamic models at the stage of preliminary solubility assessment. The article investigates predicting the solubility of pharmaceutical substances issue on the example of the technology for isolating hesperidin and glycyrrhizic acid from plant materials.Aim. Theoretical determination of the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid.Materials and methods. The PMUNIFAC and NRTL-SAC thermodynamic models were used to predict solubility. The solubility calculation for the NRTL-SAC model was performed using Aspen Properties V14 software, and for the PMUNIFAC model using PTC Mathcad Prime V6. To evaluate the results obtained using thermodynamic models, a number of experiments were carried out, the object of which was the peel of an orange (dried flavedo and albedo, the degree of grinding is 0.2–0.5 mm, the moisture content is 8 %). The quantitative content of hesperidin was determined by direct spectrophotometry at a wavelength of 290 nm. Statistical data processing was performed using Minitab v20 software (Minitab Inc., USA), differences were considered statistically significant at p < 0.05.Results and discussion. On the basis of thermodynamic models, the prediction of the solubility of hesperidin and glycyrrhizic acid was made. It has been shown that the solubility can be assessed both in the presence of solubility data according to the NRTL-SAC model, and in their complete absence according to PMUNIFAC. The correspondence of the theoretically calculated data to the experimental data confirms the correctness of the calculations of thermodynamic models. The results of the calculations are evaluated and solvents are recommended that can be used in the technology of isolating hesperidin and glycyrrhizic for the stages of degreasing, extraction and crystallization with the antisolvent.Conclusion. Using the NRTL-SAC and PMUNIFAC thermodynamic models, the dissolving power of various solvents with respect to hesperidin and glycyrrhizic acid was determined. From the calculation results, a list of solvents was built, ranked by the solubility of the studied substances in them. The resulting list can be used in the development of an industrial technology for the isolation and purification of hesperidin and glycyrrhizic acid. It is shown that the NRTL-SAC and PMUNIFAC models have good prospects for quantitative prediction of the solubility of active substances.

Keywords

• nrtl-sac
• pmunifac
• thermodynamic modeling
• solubility
• prediction
• hesperidin
• glycyrrhizic acid