Category: Formulation and Quality
Purpose: The purpose of this poster is to show how the benefits of using SFC, compared to other separation techniques like HPLC, allow for pharmaceutical degradants or impurities to be rapidly and efficiently isolated for use in further identification and or characterization experiments.
Methods: The poster will show the systematic approach we take to isolate impurities. Starting from the customer’s HPLC purity method, we develop an analytical scale SFC method by screening a selection of stationary phases and co-solvents. From the best co-solvent / stationary phase combination, a preparative SFC method is generated to the bulk material fractionated. The SFC fractions are then analyzed by the original HPLC purity method. This process is repeated until the impurity is fully purified.
Results: The results shown will walk through 2 case studies. In the 1st study, an impurity is isolated from a crude supply that contains only a very small percentage of the impurity using multiple SFC methods. The 1st method enriches the impurity to a level removing a majority of the main peak (API). This allows for a more specific method to be developed resolving the impurity form the other peaks for successful isolation. This example leverages the speed of processing in SFC vs. HPLC; through increased loading, narrow bands, and high linear solvent velocities. It is estimated this approach, compared to HPLC, is at least 5-10 fold faster.
The 2nd case study walks through an example where the impurity of interest is already enriched in a crystallization mother liquid. However, the crude supply also contains a complex mixture of other peaks. This example uses the processing speed advantage as well, but in comparison with HPLC we note that the speed of method development offers a significant additional process enhancement. SFC allows for shorter columns and higher flow rates resulting in faster method. Moreover, this translates to as many as 20 different SFC methods may be evaluated for every one HPLC scouting run.
Conclusion: We demonstrate that by using Supercritical Fluid Chromatography (SFC) in place of traditional reversed-phase and normal phase HPLC, timelines can be greatly reduced by leveraging the rapid method development cycle of SFC and the high efficiency of preparative separations. In addition, the lability of degradants during the isolation process may be minimized in common SFC solvent systems and by the collection of highly concentrated fractions.
Alexander Neue– Marlborough, Massachusetts