Evaluation of particle size distribution of salmeterol administered via metered-dose inhaler with and without valved holding chambers

Ann Allergy Asthma Immunol. 2001 Dec;87(6):482-7. doi: 10.1016/S1081-1206(10)62261-2.


Background: Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask.

Objective: This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs.

Methods: Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus.

Results: Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 microm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated.

Conclusions: In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Albuterol / administration & dosage*
  • Albuterol / analogs & derivatives*
  • Asthma / drug therapy
  • Bronchodilator Agents / administration & dosage*
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Equipment Design
  • Humans
  • Infant
  • Masks
  • Nebulizers and Vaporizers* / standards
  • Particle Size
  • Salmeterol Xinafoate


  • Bronchodilator Agents
  • Salmeterol Xinafoate
  • Albuterol