Experimental measurement – correlation of solubility and dissolution thermodynamics study of itraconazole in pure monosolvents at various temperatures

Abstract

The information about the solubility and thermodynamic properties of solution is important for pharmaceutically important processes, formulation development, and further theoretical studies. In the present study, the solid–liquid equilibrium (solubility) for itraconazole (ITC) was determined experimentally in 14 monosolvents at temperatures between 293.15 K and 318.15 K under pressure of 0.1 MPa. The mole fraction solubilities were found to increase with increasing temperatures and followed inverse trend with the polarity of selected solvents. Besides, KAT-LSER analysis was performed to study the effect of solvent. The results revealed that the solute–solvent interaction (43.94%) was much higher than that of solvent–solvent interaction (16.59%). Thermodynamic based models like van’t Hoff equation, modified Apelblat equation, Buchowski–Ksiazaczak equation, and polynomial empirical equation were applied to fit and correlate the experimental solubilities. Overall relative average deviation $(\mathit{RAD})$ and overall root-mean square deviation (${10}^4\times \mathit{RMSD}$) were observed to be minimum with the empirical polynomial equation and attained the values of 0.0033 and 0.0047, respectively. Furthermore, theoretical ideal solubilities, activity coefficients, and thermodynamic properties of dissolution including molar enthalpy, molar entropy, molar Gibbs free energy, and excess enthalpy were estimated. Ideal solubilities were projected considerably higher than experimental solubilities at each studied temperature. Thermodynamic properties of dissolution indicated that the dissolution was not a spontaneous process; observed to be endothermic (${\Delta H}_0^{\mathrm{soln}}>0)$ and enthalpy driven ${(\Delta \mathrm{S}}_0^{\mathit{soln}}>0).$ Such solid–liquid equilibrium data of ITC will be of immense help in process and formulation development in pharmaceutical sciences.

Keywords:

• Itraconazole
• solid–liquid equilibrium
• solubility correlation
• KAT-LSER model
• dissolution thermodynamic
• activity coefficient
• excess enthalpy

Acknowledgements

The authors are grateful to Marathwada Mitra Mandal’s College of Pharmacy, Kalewadi, Pune, Maharashtra, India for providing the necessary facilities to carry out the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).