PURPOSE OF THE STUDY.
To investigate the differences in 3 albuterol sulfate metered-dose inhaler (MDI) products and their particle size. The study also evaluated if use of a valved holding chamber (VHC) would impact drug delivery and/or diminish systemic adverse effects.
The study did not use human subjects, but rather examined Ventolin hydrofluoroalkane (HFA), Proventil HFA, and ProAir HFA, the 3 racemic albuterol sulfate pressurized MDI products available in the United States.
The experimental design involved a nonviable 8-stage Anderson Cascade Impactor (ACI) with a US Pharmacopeia (USP) throat model with a mean (SD) airflow rate of 28.3 (0.5) mL/min. Each of the 3 albuterol MDI products had their particle size assessed 6 times with and 6 times without spacer or holding chamber. With the use of high-performance liquid chromatography (HPLC) albuterol sulfate deposition was analyzed at each stage of the ACI.
Testing of MDI products without a VHC showed that Ventolin HFA had an inhalable dose of 21 μg and a noninhalable mean dose of 66 µg of albuterol sulfate, an inhalable fraction of 24%. In contrast, Proventil HFA had a mean inhalable dose of 40 µg and a noninhalable dose of 35 µg (58% inhalable fraction). ProAir HFA had a mean inhalable dose of 64 µg and a noninhalable dose of 42 µg, yielding a 61% inhalable fraction. All 3 of the products had inhalable doses significantly lower than their total doses. Nonetheless, there was only a significant difference (P < .01) between the mean total doses of Proventil HFA (75 µg) and ProAir HFA (107 µg). When a VHC was used, the inhalable fraction for Ventolin HFA was 94%, Proventil HFA 98%, and ProAir HFA 97%. However, the total dose for Ventolin HFA, Proventil HFA, and ProAir HFA were 25 µg, 54 µg, and 63 µg, respectively. These values were less in all 3 albuterol sulfate MDIs compared with when a VHC was not used. This indicates that larger, noninhalable particles were more likely to stick to the spacer device and are not deposited on the mouth or tongue, while the smaller inhalable particles were still delivered.
These results show a difference between the 3 products and their total dose delivered with or without spacer use. Ventolin HFA was found to deliver 2 to 3 times lower dose than Proventil HFA and ProAir HFA. The results in this study support that spacers increase the inhalable percentages of all 3 products while preventing deposition of larger, noninhalable particles on the mouth and tongue. This would likely decrease the side effect profiles on these medications.
The ability to make well-informed decisions regarding safety and efficacy of the medications we prescribe for our patients is essential. All devices do not deliver the same amounts of medication. This study delivers more justification for recommending spacer use in our patients, as they may prevent the deposition of larger particles of the inhaled medications in the mouth and decrease the potential adverse side effect profile of these medications. Although these in vitro studies add evidence to previously published findings on differences between the various albuterol sulfate MDI products, in vivo studies are needed.
- Copyright © 2017 by the American Academy of Pediatrics