Conclusion
The results of this study show that even for the relatively simple solution of a pure small-molecule drug, the collapse temperature
determined by FDM can be considered as the practically more relevant CFT for process development and optimization. The direct
observation of the collapse event and the width of the gap between Toc and Tfc can provide additional valuable information on the temperature tolerance of the sample. In the case of gentamicin sulfate,
the temperature difference is not as big as it has been reported for protein formulations, indicating low robustness of the
dried material in the microcollapse regime. Considering the great influence of small differences in product temperature on
primary drying time and product morphology, the use of freeze-dry microscopy is a substantial contribution to efficiency and
quality in the freeze-drying of small molecules.
Click here for video on the process of taking freeze-dry microscopic measurements
Acknowledgments
The authors acknowledge Hiltrud Lindenblatt, PhD, and senior scientist of life-cycle management CMC management at Merck KGaA,
for providing the gentamicin sulfate.
Henning Gieseler* is an assistant professor and group leader in the Freeze-Drying Focus Group, Division of Pharmaceutics, University of Erlangen
(Erlangen, Germany), and managing director of Gilyos GmbH, 15 Friedrich-Bergius-Ring, Wuerzburg, Germany, 97076, tel. +49
931 907 05678, info@gilyos.com
Susanne Hibler is a graduate student in the Freeze-Drying Focus Group, Division of Pharmaceutics, University of Erlangen.
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