Exploration of temperature and shelf-life dependency of the therapeutically available Insulin Detemir

Beji, Oritsegidenene; Gillis, Richard B.; Dinu, Vlad; Jiwani, Shahwar I.; Gyasi-Antwi, Philemon; Fisk, Ian D.; Meal, Andrew; Morgan, Paul S.; Harding, Stephen E.; Huang, Sha; Agugini, Giulia; Fedele, Federica; Adams, Gary G.

Abstract

© 2020 Elsevier B.V. Purpose: Insulin, in typical use, undergoes multiple changes in temperature; from refrigerator, to room temperature, to body temperature. Although long-term storage temperature has been well-studied, the short term changes to insulin are yet to be determined. Insulin detemir (IDet) is a clinically available, slow-acting, synthetic analogue characterised by the conjugation of a C14 fatty acid. The function of this modification is to cause the insulin to form multi-hexameric species, thus retarding the pharmacokinetic rate of action. In this investigation, the temperature dependence properties of this synthetic analogue is probed, as well as expiration. Methods: Dynamic light scattering (DLS) and viscometry were employed to assess the effect of temperature upon IDet. Mass spectrometry was also used to probe the impact of shelf-life and the presence of certain excipients. Results: IDet was compared with eight other insulins, including human recombinant, three fast-acting analogues and two other slow-acting analogues. Of all nine insulins, IDet was the only analogue to show temperature dependent behaviour, between 20 °C and 37 °C, when probed with non-invasive backscatter dynamic light scattering. Upon further investigation, IDet observed significant changes in size related to temperature, direction of temperature (heated/cooled) and expiration with cross-correlation observed amongst all 4 parameters. Conclusions: These findings are critical to our understanding of the behaviour of this particular clinically relevant drug, as it will allow the development of future generations of peptide-based therapies with greater clinical efficacy.

Citation

Beji, O., Gillis, R. B., Dinu, V., Jiwani, S. I., Gyasi-Antwi, P., Fisk, I. D., Meal, A., Morgan, P. S., Harding, S. E., Huang, S., Agugini, G., Fedele, F., & Adams, G. G. (2020). Exploration of temperature and shelf-life dependency of the therapeutically available Insulin Detemir. European Journal of Pharmaceutics and Biopharmaceutics, 152, 340-347. https://doi.org/10.1016/j.ejpb.2020.05.016

• Journal Article Type: Article
• Acceptance Date: May 17, 2020
• Online Publication Date: May 21, 2020
• Publication Date: Jul 1, 2020
• Deposit Date: May 29, 2020
• Publicly Available Date: May 22, 2021
• Journal: European Journal of Pharmaceutics and Biopharmaceutics
• Print ISSN: 0939-6411
• Electronic ISSN: 1873-3441
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 152
• Pages: 340-347
• DOI: https://doi.org/10.1016/j.ejpb.2020.05.016
• Keywords: Biotechnology; Pharmaceutical Science; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4529760
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0939641120301429