The solubility profile and dissolution thermodynamic properties of minocycline hydrochloride in some pure and mixed solvents at several temperatures

The dissolution process of alpha-minocycline hydrochloride in different solvent within the temperature range from 273.15 K to 313.15 K was studied by using "isothermal saturation method" under atmospheric pressure. It is found that the minocycline hydrochloride is insoluble in ethyl acetate and acetonitrile compared with alcohols. The maximum "mole fraction solubility" of minocycline hydrochloride in methanol is 2.88 x 10(-3) at 313.15 K and followed by ethanol is 1.90 x 10(-3) at 313.15 K, n-propanol is 1.23 x 10(-3) at 313.15 K, isopropanol is 2.10 x 10(-4) at 313.15 K, acetonitrile is 7.78 x 10(-5) at 313.15 K and ethyl acetate is 2.63 x 10(-5) at 313.15 K. The higher solubility of minocycline hydrochloride in alcohols could be due to their ability to form hydrogen bonds with solute molecule compared with ethyl acetate and acetonitrile. However, in mixtures of ethyl acetate (1-w) + methanol (w), the solubility values increased firstly, and then decreased with the mass fraction (w) of methanol, the maximum data is 6.07 x 10(-3) at w = 0.60 at 313.15 K, an increase about 230 fold. In dissolution process of a solute in pure or mixed, solute - solvent interactions are more significant among other interactions and should be considered in any interpretation of the solubility behaviour. In order to obtain a rough evaluation of the solute - solvent intermolecular interactions, the solvatochromic parameters of pure and mixed solvents were discussed. Moreover, the experimental solubility are correlated by the modified Apelblat equation and Jouyban-Acrees model, and the values of relative average deviation (RAD) are all less than 0.76% in pure organic solvents, and no more than 6.80% in mixtures. Besides, the results of apparent thermodynamic analysis indicates that the dissolution is an endothermic and entropy driven process. The solubility data and thermodynamic properties would be useful in the process of purification, recrystallization and dosage form design in pharmaceutical industries. (C) 2021 Published by Elsevier Ltd.