Heat Decreases Formoterol Delivery

Study objectives:Based on anecdotal reports of formoterol aggregating in mailboxes in the summer in Arizona, we examined the effect of heat on formoterol as well as on drug delivery.Design:Formoterol capsules in original blister packaging were heated to 40 to 70°C (104 to 158°F) for 3 h and at 70°C (158°F) for 15 to 180 min. Capsules were removed from packaging, and a vacuum setup was used to dispense the formoterol into a filter using the device provided by the manufacturer. The weights of the capsule predispensation and postdispensation were measured to calculate drug delivery. Measurements were compared to those of capsules not exposed to heat. For comparison, tiotropium and a combination of fluticasone propionate and salmeterol (Advair; GlaxoSmithKline; Research Triangle Park, NC) were similarly tested.Results:Visual inspection of the heated capsules revealed gross distortion as well as visible clumping of formoterol at the higher temperatures. The mean (± SEM) change in the weights of capsules that underwent heating were significantly less than those obtained from capsules that had not been heated (mean change after heating for 3 h at 70°C, 2.3 ± 0.7 vs 24.7 ± 0.6 mg, respectively; p < 0.001), indicating decreased formoterol delivery. Heat produced a dose-responsive and time-responsive decrease in formoterol delivery. One of six capsules that were subjected to temperatures as low as 40°C (104°F) for 3 h had decreased delivery, and three of six capsules subjected to a temperature of 70°C (158°F) for times as short as 30 min decreased delivery. In contrast, neither tiotropium nor fluticasone propionate/salmeterol delivery was decreased by heating for up to 3 h at 70°C (158°F). Thermometers placed in mailboxes or in car windows in mid-summer in Arizona (approximate outside temperature, 110°F [43°C]) exceeded 70°C (158°F).Conclusions:These data demonstrate that the exposure of formoterol to heat decreases drug delivery and that caution should be used when mailing, transporting or storing formoterol.