.Degradation of active drugs in medicinal vials exposed to temperature extremes encountered during military operations: the Military Medication Temperature Effect Study.

INTRODUCTION

Maintaining the activity of pharmaceuticals and preventing the accumulation of harmful degradation products during storage are essential for efficacy and safety, particularly for non-titrated medications such as antibiotics. Although manufacturers' storage instructions usually specify a target controlled temperature, military operations often occur in extreme environments with substantial temperature variability. No manufacturer provides data to guide decisions under such circumstances. This study assessed the stability of 10 medications commonly used in the Australian Defence Force (ADF) prehospital setting when subjected to operationally relevant temperatures.

METHODS

10 medications (pseudoephedrine, cefazolin, tranexamic acid, ceftriaxone, hydrocortisone, benzylpenicillin, promethazine, ketorolac, amiodarone and metoclopramide) were stored for 14 or 28 days under five conditions: -20°C, 30°C, 50°C, 30°C-50°C diurnal cycling and ambient control (24°C±1°C). Stability was assessed by recording pH, visual appearance, subvisible particle count distribution and intact content using validated physicochemical and chromatographic methods. Changes exceeding the coefficient of variation (CV) of ambient control replicates were flagged as signs of potential instability.

RESULTS

Nine of the 10 medications retained ≥90% of original content across all conditions and met criteria for stability according to visual appearance, pH and subvisible particle formation. However, after 14 days at 50°C, cefazolin content fell below this threshold (87.7%), and the CV in pH failed the acceptance criterion. Minor fluctuations above control CV were also noted for tranexamic acid, promethazine and pseudoephedrine, but no significant degradation trends emerged.

CONCLUSIONS

Most of the medications tested retained acceptable physicochemical characteristics over 28 days under conditions simulating field exposure. These findings provide preliminary support that some medications may remain suitable for use when manufacturer-recommended temperatures cannot be maintained, and resupply is unlikely. However, the single sample (n=1) study design limits confidence in the findings. Further replicated studies are required before these results should inform medicines management policy.