Stability of APIs in presence of excipients

Stability study of a weakly ionizable drug

Excipients are crucial components of most pharmaceutical formulations. In the case of a solid oral dosage formulation containing the salt form of a weakly ionizable drug, excipient selection is critical, as some excipients are known to cause salt disproportionation (conversion of salt to the free form). An in-depth understanding of the nature and rate of disproportionation is the first step towards assessing stability.

We were able to suggest an easy alternative

For a client, we performed a thorough study of 15 components in an oral drug containing an active pharmaceutical ingredient (API) and several excipients with and without the presence of a coating. In literature the disproportionation of an amine salt was studied using Raman spectroscopy. The client therefore approached us with the request to perform Raman spectroscopy on the samples. However, on looking at the molecular structure of the API we noticed the presence of an adjacent functional group that could provide a handle to study changes caused by instability. We hypothesized that the IR shift of this group should distinctly vary between the amine salt and the free amine. If so, then infrared spectroscopy (IR) could be used instead of Raman spectroscopy.

Faster and accurate results

Indeed using IR we noticed distinct difference in the IR stretch of a particular functional group of the free amine and amine salt and could perform the entire study using IR instead of Raman spectroscopy. This gave much faster and accurate results. One of the issues with Raman spectroscopy can be fluorescence. Some excipients fluoresce leading to noisy baselines which need to corrected for. This was not a problem with IR.