Effect of drug load and plate coating on the particle size distribution of a commercial albuterol metered dose inhaler (MDI) determined using the Andersen and Marple-Miller cascade impactors.
OBJECTIVE
The purpose of this study is to investigate the effect of drug load, the coating of impactor stages, and the design of cascade impactors on albuterol MDIs particle size distribution measurements. The results of the investigation will be used to explain the "loading effect" recently reported.


METHODS
Particle size distribution parameters of a commercial albuterol MDI were measured using both Andersen (AI) and Marple-Miller (MMI) Cascade Impactors, where plates were either left uncoated or coated with silicone or glycerin. A previously validated HPLC-EC method was used for the assay of albuterol collected by the impactor and in single spray content determinations.


RESULTS
Coating impactor collection plates had an impact on measured MMAD and GSD values for single puff measurements but very little or no effect for the multi puff measurements. Due to particle bounce, the percent of albuterol fine particles deposited in the filter and impactor finer stages (< 1.10 microns in AI and < 1.25 microns in MMI) in uncoated single puff experiments was much higher in comparison to either coated single puff or multi-puff (coated and uncoated) measurements.


CONCLUSIONS
Evaluation of drug load and plate coating are necessary to determine whether observed particle size distributions are representative of the generated aerosol or are the result of particle bounce and reentrainment. In order to minimize particle bounce, especially for single puff determinations, it may be useful to apply a thin layer of a sticky coating agent to the surfaces of impactor plates.
Nasr
M M
MM
US Food and Drug Administration, CDER, Division of Testing and Applied Analytical Development (DTAAD), St. Louis, Missouri 63101, USA. NASRM@DDASTL.CDER.FDA.GOV
Ross
D L
DL
Miller
N C
NC
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry*; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000420:Albuterol