Stability of sufentanil sublingual microtablets (Dzuveo) in extreme cold weather conditions: an experimental study

Introduction
Extreme cold weather environments are challenging for medication storage and delivery, particularly for injectable analgesics vulnerable to freezing and device failure. These risks may compromise pain management in austere or operational settings where temperature control cannot be maintained. Sufentanil sublingual microtablets (sold in the UK as Dzuveo) provide an oral analgesic option with manufacturer-reported sub-zero stability. Evidence describing the effects of sustained extreme cold exposure and repeated freeze–thaw cycling on chemical stability and delivery system function is limited.

Methods
We conducted a laboratory study assessing the effect of sustained freezing and repeated freeze–thaw exposure on sufentanil sublingual microtablets (30 µg active pharmaceutical ingredient). Tablets from two production batches (expiry August 2025 and July 2026) were allocated to room temperature control, static freezing at −20°C or −80°C, or repeated freeze–thaw cycling at both temperatures. Freeze–thaw cycling was designed to simulate intermittent carriage in extreme cold environments. Laboratory operators were blinded to sample allocation. The primary outcome was sufentanil mass and concentration measured using liquid chromatography–high resolution accurate mass spectrometry. Secondary outcomes included visual assessment of microtablet integrity and applicator function.

Results
60 tablets were analysed, with one weight outlier excluded from concentration-based analyses. There were no statistically significant differences in sufentanil mass or concentration between control samples and those exposed to freezing or repeated freeze–thaw cycling at −20°C or −80°C. Visual inspection identified no evidence of microtablet degradation, and all applicators functioned normally across exposure conditions.

Conclusions
Sufentanil sublingual microtablets and their delivery system maintained chemical stability and functional integrity following exposure to extreme cold temperatures and repeated freeze–thaw cycles. This laboratory study provides reassurance regarding formulation resilience in cold environments but does not assess clinical effectiveness. Further research is required to determine the impact on patient outcomes in operational or military settings.