The Effect of Temperature on the Stability of In-Use Insulin Pens

Abstract

Background Improper storage of insulin could decrease its potency. Manufacturers recommend that in-use insulin pens should be kept at between 25–30°C, but room temperature in tropical countries often exceeds this range. This study investigates the effect of temperature on the stability of basal insulin in cartridges 28 days after opening.

Methods Four different basal insulins were evaluated. Five opened pens of each insulin type were included for each of three storage conditions and 5 unopened insulin pens of each type were stored in the refrigerator as a control. The opened pens were stored for 28 days in either a refrigerator (2–8 °C), at room temperature, or in an incubator (37 °C). Each day insulin pens were mixed 20 times and 2 units were discarded to mimic daily usage. Insulin quantity was evaluated using an ultra-high-performance liquid chromatography assay.

Results The average room temperature during the study period was 29.7 °C. After 28 days, the percentage amount of insulin stored at refrigerator, room temperature or incubator, compared with control was 99.0, 99.7, 101.1% for long-acting insulin; 97.4, 97.2, 99.0% for NPH-1; 101.4, 101.5, 100.7% for NPH-2; and 98.7, 97.8, 98.5% for NPH-3. There were no statistically significant differences. However, we observed a trend toward different stability between clear insulin analog and turbid NPH insulin.

Conclusions Temperature as high as 37°C and cyclic temperature,had no effect on the stability of in-use insulin pen.

Key words

diabetes education - insulin pen - insulin stability - insulin storage - temperature effect

Publication History

Received: 04 July 2019
Received: 21 August 2019

Accepted: 09 September 2019

Article published online:
21 October 2019

• References

• 1 Sanofi -aventis, Canada, Inc . Product monograph LANTUS (2017). Available from https://www.lantus.com/-/media/EMS/Conditions/Diabetes/Brands/Lantus2/Consumer/desktop/PDF/Lantus-SoloStar-Pen-Guide.pdf?la=en
• 2 Vimalavathini R, Gitanjali B. Effect of temperature on the potency & pharmacological action of insulin. Indian J Med Res 2009; 130: 166-169
• 3 The united state pharmacopeial convention. Insulin 2013 Available from: https://www.uspnf.com/sites/default/files/usp_pdf/EN/USPNF/revisions/isophane_insulin_human_suspension.pdf
• 4 Joffe D.. Stability of Common Insulins in Pens and Vials 2011. Available from https://www.ghdonline.org/uploads/se_insulin_stability_chart.pdf
• 5 The Diabetes Association of Thailand. Instruction of Antidiabetic Drug Injection Technique for Medical Personnel. 2016
• 6 Kongmalai T, Sriwijitkamol A. Evaluation of Thai insulin-treated diabetics’ knowledge and practice of insulin pen storage. J Med Assoc Thai 2019; 102: 503-507
• 7 Storvick WO, Henry HJ. The effect of storage temperature on stability of commercial insulin preparations. Diabetes 1968; 17: 311
• 8 Albergo R, Bunting J, Belsky MK. et al. Insulin storage and injection recommendation. Diabetes Care 1992; 15: 1113-1114
• 9 Jehle PM, Clemens M, Jehle DR. et al. Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens. Lancet 1999; 354: 1604-1607
• 10 Ogle GD, Abdullah M, Mason D. et al. Insulin storage in hot climates without refrigeration: temperature reduction efficacy of clay pots and other techniques. Diabet Med 2016; 33: 1544-1553
• 11 Smith HW, Atkins LM, Binkley DA. et al. A universal HPLC determination of insulin potency. J Liq Chromatogr 1985; 8: 419-439
• 12 Farid NA, Atkins LM, Becker GW. et al. Liquid chromatographic control of the identity, purity and “potency” of biomolecules used as drugs. J Pharm Biomed Anal 1989; 7: 185-188
• 13 Moses A, Bjerrum J, Hach M. et al. Concentrations of intact insulin concurs with FDA and EMA Standards when measured by HPLC in different parts of the distribution cold chain. J Diabetes Sci Technol 2019; 13: 55-59