Study of solubility and thermodynamic properties of sildenafil citrate in the binary mixtures of N-methyl-2-pyrrolidone and ethanol at different temperatures

Abstract

Considering the low¬ water solubility of most drugs, improving this feature is one of the important steps in drug research and development. One of the simplest and oldest methods of increasing solubility is cosolvency. In addition, to predict solubility in different solvent systems, in order to save time and money, modeling with various mathematical models can be used. Aim:In the present study, the solubility and density of the sildenafil citrate in the mixture of NMP+Ethanol solvents were investigated at 5 different temperatures. Also, the correlations between measured data and different solubility models have also been investigated.Method:In the present study, the solubility is measured using shake-flask method. In this way, mass fractions of NMP and Ethanol were prepared at 10% mass intervals, and the excess amount of drug is dispensed into it, and after centrifuging the solution and proper dilution, the absorbance of the solutions was recorded by a UV spectrophotometer at a wavelength of 290 nm, and the concentration of the samples is obtained by referring to the calibration curve. This process is repeated for 5 temperatures and all data are correlated with some common cosolvency models.Results:Based on the obtained data, the solubility increases with the increase of the mass fraction of cosolvent and the temperature, so that the maximum solubility is related to the mass fraction of 1.0 of cosolvent at a temperature of 313.2 K. Conclusion :The solubility data showed an increasing trend as the temperature increased and the mass fraction of NMP solvent increased up to 1.0. Data were fitted to different models and constants were calculated for each model. In each of the models, the percentage of error was less than 9%, which indicates their high potential as drug solubility prediction models.