Study of clotrimazole solubility in in the cosolvency system of propylene glycol + water

Abstract

Clotrimazole is an imidazole derivative with a wide spectrum of antifungal activity. The bioavailability of drugs, including clotrimazole, depends on their physical and chemical properties, including lipophilicity and solubility in physiological environments. Considering the low solubility of clotrimazole in water, increasing its solubility is important. In addition to experimental works to measure the solubility of a drug in a mixture of solvents, various theoretical methods have been presented to correlate physicochemical properties. Among these methods, Joyban-Akri model is a simple model with high predictive power in a wide range of temperatures and solvent composition.Aim: Measuring the solubility of clotrimazole in the propylene glycol + water system in the temperature range of 293.2 to 313.2 K and correlating the obtained data with mathematical equations are the goals of this study.Method: In this study, shake flask method was used. In this way, the excess amount of medicine was added to vials containing propylene glycol and water in specific mass fractions. After 48 hours, the supernatant solution was centrifuged, diluted and its absorption value was recorded at 260 nm wavelength. Finally, the concentration of saturated solutions was calculated using the calibration curve. This process was repeated for 5 temperatures and the resulting data were fitted with a number of solubility models. Results:Clotrimazole drug solubility increases with increasing temperature and concentration of propylene glycol solvent. So that the highest solubility is observed in pure propylene glycol at a temperature of 313.2 K.Conclusion:The obtained data show that propylene glycol is a suitable solvent to increase the solubility of clotrimazole. In addition the resulting data has a good correlation with cosolvency models and the percentage of prediction error means that the predictive power of the model is within an acceptable range.