INHALATION OF SINGLE VS MULTIPLE METERED-DOSE BRONCHODILATOR ACTUATIONS FROM RESERVOIR DEVICES - AN IN-VITRO STUDY

Differences in inhalation technique with reservoir or spacer devices m ay affect metered-dose inhaler (MDI) dose availability to a patient. P urpose: This study examined the effect of single vs multiple actuation s of an MDI into reservoir devices on dose delivery of albuterol, with three clinically available reservoir brands. Methods: An in vitro lun g model simulated inspiration from the MDI reservoir system. Albuterol (Proventil; Schering) was delivered by MDI, with the Monaghan Aerocha mber, the Diemolding Healthcare Division (DHD) aerosol cloud enhancer (ACE), and the Schering InspirEase, using standardized volumes and ins piratory flows of 30 L min(-1). The MDI was actuated into each brand o f reservoir 1, 2, or 3 times in rapid succession, followed by a single inhalation. Aerosol dose at the reservoir mouthpiece was captured on a cotton filter, dissolved in ethanol, and measured with a spectrophot ometer at 278 nm. Results: For all three brands of reservoir, less acc umulated dose of drug is delivered with multiple actuations than with multiple single actuations each followed by inhalation. The total dose in milligrams increased significantly with two multiple actuations co mpared with one actuation in the Aerochamber and ACE (p<0.01), but not in the InspirEase (p>0.05). The Aerochamber, ACE, and InspirEase deli vered a mean total dose (SD) of 0.0264 mg (0,012), 0.0271 mg (0.007), and 0.0136 mg (0.006), respectively, with one actuation compared to 0. 0485 mg (0.011), 0.0453 mg (0.013), and 0.0218 mg (0.009) with two mul tiple actuations. The increase in total dose with three multiple actua tions was not significant compared to two actuations for any of the br ands tested (p>0.05). Although total dose increased with multiple actu ations, a decline in efficiency was seen with two and three multiple a ctuations, compared to single actuation. The dose delivered per actuat ion decreased for the Aerochamber, ACE, and InspirEase from 0.0264 mg (0.012), 0.0271 mg (0.007), and 0.0136 mg (0.006) with one actuation, to 0.0243 mg (0.006), 0.0226 mg (0.006), and 0.0109 mg (0.005), respec tively, with two multiple actuations, for losses of 8.0%, 16.6%, and 1 9.9% in dose per actuation for each brand. A further decline in delive ry per actuation to 0.0164 mg (0.001), 0.0184 mg (0.004), and 0.0097 m g (0.005) for the 3 brands, respectively, was found with 3 multiple ac tuations before inhalation. This was a loss of 37.9%, 32.1%, and 28.7% of the dose per single actuation in each brand. There was no signific ant difference between the Aerochamber and the ACE in dose availabilit y with 1, 2, or 3 actuations, but both of these brands provided signif icantly more drug than the InspirEase. Conclusion: Maximal aerosol bro nchodilator from an MDI reservoir was given by single actuations each followed by a breath. Two rapid actuations followed by a breath will g ive a significant accumulation of dose with some loss when compared to two single actuations each followed by inhalation. Three multiple act uations led to a loss of approximately one third of the drug dose obta inable with three single actuations each followed by inhalation, for a ll three brands.