Imaging Techniques to Characterize Cake Appearance of Freeze-Dried Products.

Pharmaceutically elegant lyophilisates are highly desirable implying a stable and robust freeze-drying process. To ensure homogenous and intact cake appearance after process scale-up and transfer, characterization of lyophilisates during formulation and cycle development is required. The present study investigates different imaging techniques to characterize lyophilisates on different levels. Cake appearance of freeze-dried bovine serum albumin formulations with different dextran/sucrose ratios was studied by visual inspection, three-dimensional laser scanning, polydimethylsiloxane embedding, scanning electron microscopy, and microcomputed tomography (μ-CT). The set of techniques allowed a holistic evaluation of external cake appearance and internal structure providing complementary information at macroscopic and microscopic scale. In comparison to state of the art technologies like visual inspection or scanning electron microscopy, three-dimensional laser scanning and μ-CT provided quantitative information allowing comparison of visual cake appearance. In particular μ-CT enables a global, qualitative, and quantitative characterization of external and internal cake structure with a single measurement detecting heterogeneities of lyophilisates. We even demonstrated the use of noninvasive μ-CT for qualitative imaging of internal cake structure through the glass vial. Providing meaningful characterization of the entire lyophilisate, μ-CT can serve as a powerful tool during development of freeze-drying cycles, process scale-up, and transfer.