Assessment of physical stability of different forms of cefadroxil at high humidities

The physical state of amorphous anhydrous, crystalline anhydrous and monohydrous forms of cefadroxil was verified by a variety of analytical methods. The batches of crystalline anhydrates showed some deviation in thermal analysis and X-ray diffraction measurements, but these were difficult to quantify. When the stability ranges were studied with isothermal microcalorimetry, the anhydrous forms transformed to monohydrate at high humidities. The differences in moisture behavior of crystalline anhydrous batches were found to be due to the amorphous content (ca. 10%) in one batch. The crystallization mechanism was deduced using microcalorimetry, gravimetrical moisture uptake measurements and optical microscopy, and was found to be cooperative, consisting of crystal transition and parallel expulsion of excess water. In addition, the corresponding transition heats were calculated. Calculation of the enthalpy value for the crystallization of the amorphous form was complicated because of the parallel processes. The amount of desorbed water and the accompanying heat was calculated from the gravimetric and microcalorimetric measurements, respectively. (C) 1998 Elsevier Science B.V. All rights reserved.