Solid state compatibility studies with tablet excipients using non thermal methods

Compatibility between two new active pharmaceutical ingredients (API) and several pharmaceutical excipients used in solid formulations has been investigated by FT-IR and HPLC following storage under two different conditions. Compatibility was investigated by storage at isothermal stress conditions for (i) 3 days and subsequently analysed by FT-IR and (ii) 12 weeks of storage and analysis by HPLC. For the majority of the examined excipients a large degradation measured by HPLC after 12 weeks storage was also detected by FT-IR following storage at isothermal stress conditions for 3 days, i.e. there was a general agreement between the results obtained by the two protocols. Further, the FT-IR method showed clear incompatibility with three excipients where no degradation products were detected by HPLC, but where a significant decrease in the API quantified by the HPLC assay, was observed. The accelerated method thus showed a clear advantage: incompatibility found after 12 weeks using HPLC was seen after 3 days with FT-IR. Furthermore, FT-IR provides an insight into structural changes not seen with HPLC. This is exemplified by the desalting of a hydrogen bromide salt of one of the two compounds, which might lead to changes of the intrinsic dissolution rate and potentially affect the bioavailability of the API. (C) 2011 Elsevier B.V. All rights reserved.