Chest
Volume 109, Issue 4, April 1996, Pages 969-974
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Clinical Investigations: Airways Irways
Inhalation of Single vs Multiple Metered-Dose Bronchodilator Actuations from Reservoir Devices: An In Vitro Study

https://doi.org/10.1378/chest.109.4.969Get rights and content

Differences in inhalation technique with reservoir or spacer devices may affect metered-dose inhaler (MDI) dose availability to a patient.

Purpose

This study examined the effect of single vs multiple actuations of an MDI into reservoir devices on dose delivery of albuterol, with three clinically available reservoir brands.

Methods

An in vitro lung model simulated inspiration from the MDI reservoir system. Albuterol (Proventil; Schering) was delivered by MDI, with the Monaghan Aerochamber, the Diemolding Healthcare Division (DHD) aerosol cloud enhancer (ACE), and the Schering InspirEase, using standardized volumes and inspiratory flows of 30 L min−1. The MDI was actuated into each brand of 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 spectrophotometer at 278 nm.

Results

For all three brands of reservoir, less accumulated 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 compared with one actuation in the Aerochamber and ACE (p<0.01), but not in the InspirEase (p>0.05). The Aerochamber, ACE, and InspirEase delivered 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 multiple actuations. The increase in total dose with three multiple actuations was not significant compared to two actuations for any of the brands tested (p>0.05). Although total dose increased with multiple actuations, a decline in efficiency was seen with two and three multiple actuations, compared to single actuation. The dose delivered per actuation 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), respectively, with two multiple actuations, for losses of 8.0%, 16.6%, and 19.9% in dose per actuation for each brand. A further decline in delivery per actuation to 0.0164 mg (0.001), 0.0184 mg (0.004), and 0.0097 mg (0.005) for the 3 brands, respectively, was found with 3 multiple actuations 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 significant difference between the Aerochamber and the ACE in dose availability with 1, 2, or 3 actuations, but both of these brands provided significantly more drug than the InspirEase.

Conclusion

Maximal aerosol bronchodilator from an MDI reservoir was given by single actuations each followed by a breath. Two rapid actuations followed by a breath will give a significant accumulation of dose with some loss when compared to two single actuations each followed by inhalation. Three multiple actuations led to a loss of approximately one third of the drug dose obtainable with three single actuations each followed by inhalation, for all three brands.

Section snippets

In Vitro Lung Model

An in vitro model of patient use of the MDI spacer assembly was used to assess the amount of β-agonist drug available with single vs multiple actuations of an MDI (Fig 1). Inspiratory breathing was simulated by connecting the mouthpiece of the MDI spacer assembly to one side of a dual-chambered test lung, with a one-way Rudolph valve to route the gas inspired from the reservoir out to the room on exhalation. The other side of the test lung was inflated by a ventilator (Nellcor-Puritan Bennett

Results

For all devices tested, ambient temperature averaged 19.9°C with an SD of 0.21, and a range of 19.6 to 20.1°C. Relative humidity was 62.4%, with an SD of 6.42% and a range of 54 to 69.7%.

Table 1 summarizes the total doses measured at the reservoir mouthpiece for all three brands of reservoir, with each of the single and multiple actuation techniques. There were significant differences overall across brands of reservoir (p=0.001) and across numbers of actuations (p<0.001) with respect to dose

Discussion

Although the availability and use of reservoir devices offers the possibility of simplifying MDI use for subjects as far as hand-breathing coordination is concerned, the use of such devices also introduces further possible permutations in the aerosol delivery system. One such variation is the introduction of multiple actuations into a reservoir device, followed by a single inhalation from the device, to obtain the dose to the lung. Our investigation of this technique found that the use of two

Conclusion

Based on the results obtained in our study, we conclude that the maximal amount of aerosol albuterol from an MDI reservoir combination will be obtained using a single actuation followed by inhalation. However, the use of two actuations in rapid succession (ie, within seconds) followed by inhalation can give an increase in total dose, with some loss of efficiency. Three actuations followed by inhalation gives less increase in total dose compared to the double actuation, with greater loss in

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This study was funded by a research grant from Diemolding Healthcare Division, Canastota, NY. The authors have no financial or other interest in the products investigated.

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