A new approach to accelerated drug-excipient compatibility testing.

The purpose of this study was to develop a method of qualitatively predicting the most likely degradants in a formulation or probing specific drug-excipient interactions in a significantly shorter time frame than the typical 1 month storage testing. In the example studied, accelerated storage testing of a solid dosage form at 50 degrees C, the drug substance SB-243213-A degraded via the formation of two oxidative impurities. These impurities reached a level of 1% PAR after 3 months. Various stressing methods were examined to try to recreate this degradation and in doing so provide a practical and reliable method capable of predicting drug-excipient interactions. The technique developed was able to mimic the 1-month's accelerated degradation in just 1 hr. The method was suitable for automated analysis, capable of multisample stressing, and ideal for use in drug-excipient compatibility screening.

An automated workstation for forced degradation of active pharmaceutical ingredients.

This article describes a system capable of performing and analysing multiple degradation experiments on drug substances as part of the process of developing stability indicating separations methods. Qualitative data are generated on the significant primary degradation processes of the drug of interest. Ten samples are refluxed with stirring in a single heating block. The robot arm is equipped with a sampling device capable of removing aliquots, during the reflux experiment, and transferring them to an HPLC injector. On-line analysis using fast HPLC with diode array and electrospray mass spectrometric detection allows identification of degradants. The methods described offer a significant time savings compared to the previously applied manual approach, and also provide data from multiple time points for each reaction. This increased knowledge about the progress of the reaction aids us in focussing efficiently on the primary degradation processes.