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) 3days and subsequently analysed by FT-IR and (ii) 12weeks of storage and analysis by HPLC. For the majority of the examined excipients a large degradation measured by HPLC after 12weeks storage was also detected by FT-IR following storage at isothermal stress conditions for 3days, 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 12weeks using HPLC was seen after 3days 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.