As physical characterization of pharmaceuticals becomes more of a focus, analytical techniques must be able to provide data that is representative of the materials being analyzed. Companies are implementing Quality by Design (QbD) and Process Analytical Technologies (PAT) initiatives to ensure robustness of formulas, processes, and products. Lyophilized products have key areas where these initiatives can play roles in product and process knowledge. Measurement of the surface area of lyophilized cakes provides valuable information on process capability and product consistency. BET surface area analysis of lyophilized products currently requires manipulation of the cake prior to testing to introduce the sample into the instrument sample tubes. This type of sample preparation technique for BET surface area testing may introduce error resulting in the lack of repeatability and robustness of the analysis and possible misrepresentation of the true surface area of the sample. Also, since manipulation is destructive to the sample, no further testing can be performed.
Possible variability stemming from non-standardized extraction techniques for removing cakes from their vials may lead to less reliable surface area data. We have developed a special prototype lyophilization vial holder apparatus that attaches to the Micromeritics ASAP 2420 Surface Area and Porosity Tester that will allow for non-destructive, intact lyophilized cake testing of surface area. In this preliminary study, we have found that surface area measurements of intact lyophilized cakes are approximately 35 – 55% less than the surface area of the same samples that have been manipulated during preparation. Further development of this product enhancement will lead to an invaluable characterization technique for lyophilized products during product development, scale-up, and as an implementable PAT tool for control of this critical process parameter.