Determination of solubility of sildenafil citrate in propylene glycol + 2-propanol and N-methyl pyrrolidone + water: Comparing solubilization power of aqueous or non-aqueous mixtures

Abstract

For identifying the solubilization power of aqueous and non-aqueous solvent mixtures for sildenafil citrate (SLC), its solubility was determined in four mono-solvents of propylene glycol, 2-propanol, N-methyl pyrrolidone and water along with the binary solvent mixtures of propylene glycol + 2-propanol and N-methyl pyrrolidone + water at 293.2 to 313.2 K and at pressure of 85 kPa. Among the neat organic solvents and also water, N-methyl pyrrolidone presented a high solubilization power for SLC (8.66 × 10-2 at 313.2 K) and its aqueous binary mixtures had also a more ability to solubilize the drug in compared with the binary (propylene glycol + 2-propanol) mixtures (with the highest value of 4.96 × 10–4 at 313.2 K). Besides, increasing the solubility of SLC with raising temperature illustrated that its dissolution in the aforementioned mixtures was endothermic. The equilibrium solid phase crystal of SLC was also characterized with X-ray powder diffraction analysis to identify no polymorphic transformation, solvate formation or crystal transition during the whole solvent crystallization process. Moreover, the experimental mole fractions were modelled by used commonly cosolvency models and regressed the model parameters. The back-calculated mole fractions of SLC by cosolvency models shown a better agreement with the experimental data (overall mean percentage deviation (OMPD) ≤ 7.6 %) and Jouyban-Acree model as a function of temperature and solvent compositions had the best performance (MPD of 3.2 %). Furthermore, the solubility data sets of SLC in 7 binary solvent mixtures were collected from the literature and correlated with the Jouyban-Acree model and its derivates, the OMPDs for the back-computed solubility indicating the generally trained models, especially Jouyban-Acree-Abraham model (MPD of 24.2 %), had an acceptable ability in the prediction of SLC solubility and can be useful in the pharmaceutical industry. Finally, apparent thermodynamic properties of Gibbs free energy, standard enthalpy and entropy of the dissolution processes were also investigated.