Heat decreases formoterol delivery.
OBJECTIVE
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.


METHODS
Formoterol capsules in original blister packaging were heated to 40 to 70 degrees C (104 to 158 degrees F) for 3 h and at 70 degrees C (158 degrees 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 degrees 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 degrees C (104 degrees F) for 3 h had decreased delivery, and three of six capsules subjected to a temperature of 70 degrees C (158 degrees 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 degrees C (158 degrees F). Thermometers placed in mailboxes or in car windows in mid-summer in Arizona (approximate outside temperature, 110 degrees F [43 degrees C]) exceeded 70 degrees C (158 degrees 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.
Robbins
Richard A
RA
Pulmonary and Critical Care Medicine, Carl T. Hayden VA Medical Center, 650 East Indian School Rd, Phoenix, AZ 85012, USA. Richard.Robbins2@med.va.gov
Thomas
Allen R
AR
Proctor
Lynda M
LM
Hoyt
Jeffrey C
JC
Hayden
John M
JM
D000280:Administration, Inhalation; D001249:Asthma / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D064420:Drug-Related Side Effects and Adverse Reactions; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D012680:Sensitivity and Specificity
D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068759:Formoterol Fumarate