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

Authors
  • Oddone, Irene1
  • Arsiccio, Andrea1
  • Duru, Chinwe2
  • Malik, Kiran2
  • Ferguson, Jackie3
  • Pisano, Roberto1
  • Matejtschuk, Paul4
  • 1 Department of Applied Science and Technology, Politecnico di Torino, 24 corso Duca degli Abruzzi, Torino 10129, Italy. , (Italy)
  • 2 Standardisation Science Section, Analytical and Biological Sciences Division, National Institute for Biological Standards and Control, Blanche Lane, Medicines & Healthcare Products Agency, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • 3 Biotherapeutics Division, National Institute for Biological Standards and Control, Medicines & Healthcare Products Agency, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK.
  • 4 Standardisation Science Section, Analytical and Biological Sciences Division, National Institute for Biological Standards and Control, Blanche Lane, Medicines & Healthcare Products Agency, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Pharmaceutical Sciences
Publisher
Elsevier
Publication Date
Jan 01, 2020
Volume
109
Issue
1
Pages
254–263
Identifiers
DOI: 10.1016/j.xphs.2019.04.014
PMID: 31002810
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

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