The effects of heat and freeze-thaw cycling on naloxone stability

Abstract

Purpose The availability of take home naloxone (THN) was increased for Canadians in 2016, including access to kits via pharmacies. Unlike typical over-the-counter (OTC) and prescription drugs, THN kits may be stored in non-standard conditions, including in vehicles, backpacks, and out of doors. To evaluate whether these non-standard storage conditions affect stability, we investigated the impact of heat and freeze-thaw cycling on naloxone hydrochloride stability. Methods To assess the effect of heat, naloxone hydrochloride ampoules were exposed to 80 °C in a temperature-controlled oven for 8 h followed by 16 h at room temperature. To assess the effect of freeze-thaw cycles, naloxone hydrochloride ampoules were exposed to − 20 °C for 16 h followed by 8 h at 4 °C. The impact of these conditions on naloxone hydrochloride stability was evaluated each day for 1 week and after 2 and 4 weeks. The concentration of remaining naloxone hydrochloride was quantified using high-performance liquid chromatography (HPLC). Naloxone hydrochloride ampoules stored at room temperature served as the experimental control. Results Naloxone hydrochloride ampoules exhibit no changes in drug concentration following exposure to heat or freeze-thaw cycles for up to 28 days compared to ampoules maintained at room temperature (as indicated in the product monograph). Conclusions Naloxone hydrochloride remains chemically stable following exposure to heat or freeze-thaw cycles after 28 days. If THN kits are stored in non-standard conditions (for up to 28 days) the active naloxone is likely to remain stable. Despite this, pharmacists should continue to emphasize the importance of appropriate storage of THN kits to ensure optimal efficacy should naloxone administration be required in an emergency situation. Electronic supplementary material The online version of this article (10.1186/s12954-019-0288-4) contains supplementary material, which is available to authorized users.

Using qualitative system dynamics modeling to understand overdose bystander behavior in the context of Connecticut’s Good Samaritan Laws and identify effective policy options

“…For example, CT state law dictates that naloxone vending machines located outdoors (and therefore available 24/7) be temperature-regulated in accordance with commercial storage suggestions [ 70 ]. However, laboratory experiments have shown that even extreme temperatures far above or below the suggested storage limits do not reduce the potency of naloxone [ 71 ].…”

Clinical Pharmacokinetics and Pharmacodynamics of Naloxone

“…The AUC inf ratio was 1.08 in favor of the dry powder, indicating about 8% higher bioavailability than for the comparator Narcan nasal spray. Powder has an advantage in cold climate zones, since it does not freeze (although extremes of cold temperature appear not to damage naloxone [ 82 ]).…”

Frequently asked questions about naloxone: Part 3

“…Naloxone has been shown to be stable when frozen and thawed between the temperatures of −20 to 4°C or at high temperatures of 80°C. 2 Although naloxone dosage forms normally carry an expiry date of 2 years, a recent study showed that naloxone for injection that had been expired for 30 years still contained more than 90% of active naloxone with limited degradation. 3 Pharmacists should routinely offer replacement kits to patients as their kits expire.…”