Comparison between dehydration and desolvation kinetics of fluconazole monohydrate and fluconazole ethylacetate solvate using three different methods

It was of interest to study the dehydration and the desolvation of fluconazole monohydrate and ethyl acetate solvate respectively and also to determine the kinetics of dehydration and desolvation using thermogravimetry (TGA). Fluconazole monohydrate and ethyl acetate solvate were prepared by crystallization in water and in ethyl acetate solvent respectively. The dehydration and the desolvation processes were characterized by differential scanning calorimetry, thermogravimetry, powder X-ray diffractometry, and Fourier transform infrared spectroscopy. The weight changes of the fluconazole monohydrate and ethyl acetate solvate samples were monitored by isothermal TGA. Kinetic analyses of isothermal TGA data were done using model dependent and model independent methods. Various heating rates were also employed in different TGA samples, in order to apply the Ozawa method to determine the kinetic parameters. Eighteen solid-state reaction models were used to interpret the isothermal TGA experiments. Based on statistics, the three-dimensional phase boundary reaction model provided the best fit of the monohydrate data while the three-dimensional diffusion model provided the best fit for the ethyl acetate solvate data. The activation energy (Ea) values derived from rate constants of the aforementioned models were 90 ± 11 and 153 ± 11 kJ/mol for fluconazole monohydrate and ethyl acetate solvate respectively. Model independent analysis and the Ozawa method were also applied to the experimental results. Based on the results obtained from the model dependent, model independent and the Ozawa method, the mechanisms of the dehydration and the desolvation were determined.