Influence of Temperature on Insulin Degradation when shipped via Mail Service

Abstract

OBJECTIVES: The objective of this study was to investigate the effects of temperature excursions on insulin during standard shipping from mail-order pharmacies. METHODS: Twelve vials of insulin (six of regular and six of neutral protamine hagedorn (NPH)) were sampled at baseline and then the six experimental vials (three regular and three NPH) were shipped through the mail system from a Tucson, Arizona post office to a Tucson, Arizona residence. The other six vials were used as controls and left in a refrigerator at 5°C. Samples were taken daily and then measured for degradation using high performance liquid chromatography (HPLC). Also, samples from control vials were put in a lab oven at a constant temperature of 48°C and analyzed at Day 0 and Day 2. RESULTS: Temperatures spiked daily to near or over 50°C with a peak of 51.5°C. The low temperature never dropped under 21°C. The area under the curve (AUC) for each individual sample drawn was used to calculate a percentage of its original concentration with Day 1 set as 100%. On Day 6, both experimental vials and control vials had similar results and were within 10% of the original concentrations measured. In the oven, NPH samples that were heated for two days lost about 4% of its concentration while the regular insulin sample lost 14%. Particle sizing data of regular insulin heated in the oven was consistent with this HPLC data, and showed significant shifts in peak position. CONCLUSIONS: Insulin appears to maintain its stability after being shipped through the mail and remaining in a mailbox for an additional five days at high summer temperatures in Arizona. However, when exposed to constant high temperatures in a laboratory oven, heat appears to affect its stability.