Extended Hildebrand Solubility Approach: Prediction and correlation of solubility of itraconazole in triacetin: water mixtures at 298.15K

INTRODUCTION: Context:
The solubility predictive methods based upon physicochemical properties of drug and solvent are of utmost importance in the design, development and optimization of various pharmaceutically important processes.
Aims:
To explore the suitability of empirical approach of Extended Hildebrand Solubility Approach (EHSA) to predict and correlate the solubility of crystalline drug itraconazole (ITRA) in triacetin: water mixtures.

METHODS: The physicochemical properties of ITRA like fusion enthalpy, solubility parameter, and ideal mole fraction solubility were estimated. The solubilities of ITRA in mixed solvent blends comprised of triacetin: water were determined at 298.15K. Theoretical solubilities were back calculated using polynomial regression equation of interaction energy parameter 'w' as a function of solubility parameter (δ_1) of solvent mixture. Similarly, the solubilities were predicted with direct method based on use of logarithmic experimental solubilities (〖logX〗_2) against solubility parameter (δ_1) solvent mixture. The predictive capabilities of both EHSA and direct method were compared using mean percent deviations.
RESULTS: The solubility of ITRA was increased in all the triacetin: water blends and was highest in the blend where solubility parameter of ITRA equaled with that of solvent mixture. The prediction capacities of direct method (mean % deviation was -1.89%) were better than EHSA (mean % deviation was 9.76%) in the fifth order polynomial regression equation.
DISCUSSION AND CONCLUSION: The results indicated that solubility of any crystalline solute can be adequately predicted and correlated with the mere knowledge of physicochemical properties and EHSA. The information obtained would be of help in process and formulation development.