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.

The Effect of high temperature on the stability of basal insulin in a pen: a randomized controlled, crossover, equivalence trial

“…First, it was conducted under an isothermal temperature condition rather than a cyclic temperature condition, and no insulin was withdrawn during the 21 days, which would more closely resemble a natural ambient environment and real-life practice. However, Kongmalai et al 12 reported no significant difference in insulin stability between fluctuating RTs and an isothermal temperature in an incubator (37°C). Second, to test the biological activity of heated insulin in humans, the insulin in our study was incubated for only 21 days instead of the usual 4-week period of use.…”

“…This study’s in vitro and in vivo results affirm the outcome of our previous experiment, namely that basal insulin in a pen retains its potency and biological activity after being stored at temperatures as high as 37°C for 28 days. 12 …”

“…Nevertheless, our previous study showed that insulin incubated at 37°C for 28 days retained its stability. 12 Third, only basal insulin glargine was investigated. However, Kaufmann et al 13 studied various types of human (rapid, NPH, mixed) and analog (lispro, mixed lispro, aspart, glargine) insulin, and the results of the insulin types were comparable.…”

“…In addition, insulin glargine (Lantus; Sanofi SA, Paris, France) was studied because a previous publication demonstrated that it had the best stability after storage at a high temperature compared with other basal insulins. 12 For the high temperature (HT) insulin pen group, the pens were stored in an incubator at 37°C for 21 days before being used. As for the refrigerated insulin pen group, unopened pens were kept in a refrigerator at 2°C–8°C until their first use.…”

“…Based on their findings, the authors concluded that insulin should be used within 2 weeks after opening in settings where insulin cannot be stored at the recommended temperature. In 2019, Kongmalai et al 12 investigated the stability of in-use basal insulin in pen devices (glargine and three commercialized formulations of Neutral Protamine Hagedorn (NPH)). Comparisons were made over 28 days for three conditions: RT (range: 25.5°C–37.1°C), refrigerator storage (range: 2°C–8°C), and incubator storage (37°C).…”