Physical characterization of erythromycin dihydrate, anhydrate and amorphous solid and their dissolution properties.

Abstract

Three erythromycin solids were characterized. In differential scanning calorimetry (DSC), the anhydrate exhibited only a melting endotherm at 193°C. The dihydrate was desolvated at temperatures between 59 and 105°C and liquefied at 124-130°C. The dehydration product remained crystalline up to 124°C (polarizing microscopic observation). When the dihydrate was heated at 135°C and cooled to room temperature, an amorphous solid having a glass transition temperature of 106°C was produced. The monohydrate reported by Allen et al. was found in this study to be a desolvation product of the chloroform solvate. The aqueous solubilities for the dihydrate and the anhydrate were determined by a conventional method, while that for the amorphous solid was estimated by measuring the dissolution rate by means of a rotating disk method. The temperature dependence of solubility for each form was such that the solubility increased with decrease in temperature. The heats of solution increased with temperature and the plots against temperature for the three forms could be fitted to a straight line. The slope of the plot appeared to be identical among the three forms. This result suggested that the above peculiar temperature dependence of solubility might result from some intermolecular interaction in the aqueous solution.