A study of the differences between two amorphous spray-dried samples of cefditoren pivoxil which exhibited different physical stabilities.

The objective of this study was to investigate the reasons for the difference in physical stability of two amorphous cefditoren pivoxil samples that had been prepared using spray drying at inlet-air temperatures of 40 degrees C (SD-A) and 100 degrees C (SD-B). The two samples appeared amorphous by powder X-ray diffraction and had indistinguishable glass transition temperatures. Despite the fact that glass transition is often regarded as an indicator of the stability of amorphous forms, crystallisation was observed for SD-A, but not for SD-B, during storage at 60 degrees C and 81% relative humidity (RH). Gravimetric water sorption data demonstrated very similar water sorption until high RH values, at which point SD-A sorbed more water than did SD-B. The values of the dispersive, acidic (K(A)) and basic (K(D)) components of surface energy of the spray-dried samples were obtained using inverse gas chromatography (IGC), in the dry state and after equilibration with different RH environments. The data showed that the two amorphous samples had different surface properties and that the effect of sorbed water on these samples was also different. It is concluded that the two samples did not have long-range order, but had differences in the orientation of molecules at the surface, which were significant enough to alter the stability when the samples were stressed with water vapour and high temperature storage. IGC proved a valuable tool with which to study changes in the surface properties of amorphous materials.