Ternary phase diagrams and metastable zone width of azithromycin in water–acetone solvent mixtures

The transition water activity of azithromycin in water–acetone solvent mixtures at temperatures 293.15 K, 298.15 K, 303.15 K and 308.15 K was determined under atmospheric pressure, and the ternary phase diagrams for the system of water–azithromycin–acetone at varying temperature were described. Results showed that azithromycin monohydrate can be obtained by lowering the water activity and the transition water activity in acetone–water solvent mixtures at temperatures (293.15 K, 298.15 K, 303.15 K and 308.15 K) was 0.17, 0.21, 0.242 and 0.287, which increased with temperature. Besides, the metastable zone width (MSZW) of azithromycin dihydrate in water–acetone solvent mixtures was measured by laser method. The effect of initial temperature and cooling rate on MSZW of azithromycin dihydrate was studied. It was observed that the MSZW decreases with the increase in initial temperature. Nevertheless, the MSZW becomes wider by enhancing the cooling rate. All the results are of great importance to develop a crystallization process for manufacturing azithromycin hydrate and could be helpful to other solvate transformation research.