Vacuum-Induced Surface Freezing for the Freeze-Drying of the Human Growth Hormone: How Does Nucleation Control Affect Protein Stability?

In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Si...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2020-01, Vol.109 (1), p.254-263
Main Authors: Oddone, Irene, Arsiccio, Andrea, Duru, Chinwe, Malik, Kiran, Ferguson, Jackie, Pisano, Roberto, Matejtschuk, Paul
Format: Article
Language:English
Subjects:
biopharmaceutical characterization
Calorimetry, Differential Scanning
Chemistry, Pharmaceutical
Chromatography, Gel
Crystallization
Freeze Drying - methods
freeze-drying
Freezing
HPLC
Human Growth Hormone - chemistry
Mannitol - chemistry
nucleation
protein aggregation
protein formulation
Protein Stability
Surface Properties
Technology, Pharmaceutical - methods
Trehalose - chemistry
Vacuum
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Summary:In the present work, the effect of controlled nucleation on the stability of human growth hormone (hGH) during freeze-drying has been investigated. More specifically, the vacuum-induced surface freezing technique has been compared to conventional freezing, both with and without an annealing step. Size exclusion chromatography and cell-based potency assays have been used to characterize the formation of soluble aggregates and the biological activity of hGH, respectively. The results obtained indicate that controlled nucleation has a positive effect on both cycle performance and product homogeneity because of the formation of bigger ice crystals, and characterized by a narrower dimensional distribution. From the point of view of hGH stability, we observed that vacuum-induced surface freezing is not detrimental to the biological activity of the protein, or aggregate formation. In addition, the effect of 2 different formulations, including trehalose or cellobiose, on protein preservation was also considered for this study.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2019.04.014