Changes in surface properties by granulation and physicochemical stability of granulated amorphous cefditoren pivoxil with additives

The evaluation of the physicochemical stability of granules of amorphous cefditoren pivoxil (CDTR-PI), alone or with polymers, demonstrated that granulated amorphous CDTR-PI with hydroxypropyl methylcellulose was the most stable. We measured glass transition temperature by differential scanning calorimetry (DSC). The molecular mobility of the whole granules did not change, and it was not consistent with the results of the evaluation of physicochemical stability. Peak shifts were observed in IR spectra of amorphous CDTR-PI with polymers after granulation, and the shifts were similar to those observed for spray-dried samples. Furthermore, the shifts were not observed after the granules were ground. Acid-base parameters, which were also measured by inverse gas chromatography (IGC), changed after granulation. These results suggested that on the surface of the granules, CDTR-PI and the polymers would be mixed monomolecularly, as in the spray-dried samples. The changes in the molecular state of a drug when mixed monomolecularly with a polymer on the surface of granules were successfully confirmed by IGC and IR. (C) 2004 Elsevier B.V. All rights reserved.