Exploration of temperature and shelf-life dependency of the therapeutically available Insulin Detemir
| Autor: | Paul S. Morgan, Vlad Dinu, Oritsegidenene Beji, Ian D. Fisk, Sha Huang, Giulia Agugini, Andrew Meal, Richard B. Gillis, Stephen E. Harding, Philemon Gyasi-Antwi, Federica Fedele, Shahwar I. Jiwani, Gary G. Adams |
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| Rok vydání: | 2020 |
| Předmět: |
Drug Storage
medicine.medical_treatment Pharmaceutical Science 02 engineering and technology Shelf life 030226 pharmacology & pharmacy Light scattering Synthetic analogue Excipients 03 medical and health sciences 0302 clinical medicine Insulin Detemir Dynamic light scattering Pharmacokinetics medicine Hypoglycemic Agents Clinical efficacy Insulin detemir Chemistry Insulin Temperature General Medicine 021001 nanoscience & nanotechnology Biophysics 0210 nano-technology Biotechnology medicine.drug |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 152:340-347 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2020.05.016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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