Characterization of a laboratory-scale container for freezing protein solutions with detailed evaluation of a freezing process simulation

Journal of Pharmaceutical Sciences
Ulrich RoesslBernd Nidetzky

Abstract

A 300-mL stainless steel freeze container was constructed to enable QbD (Quality by Design)-compliant investigations and the optimization of freezing and thawing (F/T) processes of protein pharmaceuticals at moderate volumes. A characterization of the freezing performance was conducted with respect to freezing kinetics, temperature profiling, cryoconcentration, and stability of the frozen protein. Computational fluid dynamic (CFD) simulations of temperature and phase transition were established to facilitate process scaling and process analytics as well as customization of future freeze containers. Protein cryoconcentration was determined from ice-core samples using bovine serum albumin. Activity, aggregation, and structural perturbation were studied in frozen rabbit muscle l-lactic dehydrogenase (LDH) solution. CFD simulations provided good qualitative and quantitative agreement with highly resolved experimental measurements of temperature and phase transition, allowing also the estimation of spatial cryoconcentration patterns. LDH exhibited stability against freezing in the laboratory-scale system, suggesting a protective effect of cryoconcentration at certain conditions. The combination of the laboratory-scale freeze contain...Continue Reading

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Citations

Apr 10, 2019·Polymers·Tai-Hsi FanRobin Bogner
Jan 26, 2021·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Brigitte StephanSilja Bühler
Apr 27, 2021·Frontiers in Bioengineering and Biotechnology·Dennis Weber, Jürgen Hubbuch
May 14, 2021·AAPS PharmSciTech·Bruna MinatoviczBodhisattwa Chaudhuri
May 31, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Marieke E Klijn, Jürgen Hubbuch
Jun 26, 2021·Biotechnology and Bioengineering·Dennis WeberJürgen Hubbuch
Aug 19, 2014·Bioconjugate Chemistry·Ailing FuVincent M Rotello

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