Lyophilization cycle design for highly concentrated protein formulations supported by micro freeze-dryer and heat flux sensor.

Autor: Carfagna M; Coriolis Pharma Research GmbH, Fraunhoferstrasse 18 b, 82152 Martinsried, Germany; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstrasse 5, Ludwig-Maximilians-Universitaet München, D-81377 Munich, Germany., Rosa M; Coriolis Pharma Research GmbH, Fraunhoferstrasse 18 b, 82152 Martinsried, Germany., Hawe A; Coriolis Pharma Research GmbH, Fraunhoferstrasse 18 b, 82152 Martinsried, Germany. Electronic address: Andrea.Hawe@coriolis-pharma.com., Frieß W; Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstrasse 5, Ludwig-Maximilians-Universitaet München, D-81377 Munich, Germany.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Aug 25; Vol. 643, pp. 123285. Date of Electronic Publication: 2023 Jul 31.
DOI: 10.1016/j.ijpharm.2023.123285
Abstrakt: High-concentration protein formulations (HCPFs) represent a common strategy and freeze-drying can mitigate the stability challenges of HCPFs. In general, an in-depth characterization of the lyophilization process is essential to not impair the product quality by inappropriate process parameters. The aim of this study was to create a primary drying design space for lyophilized HCPFs by utilizing the heat flux sensor (HFS) integrated in a MicroFD with a minimum number of cycles and product vials. All the necessary data to obtain the design space were determined starting from only two lyophilization cycles, each holding 19 vials. The vial heat transfer coefficient (Kv) was determined by the HFS and compared to gravimetric values. The results indicate a consistant offset between the HFS and the gravimetry based values for annealed samples with higher protein content. This work highlights a possibility of integrating new technologies, the HFS and the MicroFD to generate a design space for lyophilization of HCPFs, which enables to implement a QbD approach at minimal material and time investment.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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