PMID- 28846482
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20180720
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 30
IP  - 6
DP  - 2017 Dec
TI  - Valved Holding Chambers and In Vitro Metered Dose Inhaler Performance: Effects of 
      Flow Rate and Inhalation Delay.
PG  - 399-410
LID - 10.1089/jamp.2015.1283 [doi]
AB  - BACKGROUND: Multiple factors may influence the performance of a metered dose 
      inhaler (MDI) when used with a valved holding chamber (VHC or "spacer"). METHODS: 
      Andersen Cascade Impactor measurements were conducted for three MDI products and 
      two different VHCs using a specially designed system that accommodated variable 
      delay times between MDI actuation and introduction of the aerosol into the 
      impactor, and allowed reduced flow through the VHC while the impactor was 
      operated at 28.3 L/min. Deposited drug mass and aerodynamic particle size 
      distribution were determined using validated high-performance liquid 
      chromatography (HPLC) methods. A two-level, three-factor full-factorial design of 
      experiments (DOE) design was applied to assess the influences of VHC type, flow 
      rate, and inhalation delay on a total of seven performance characteristics for 
      each MDI product. An experiment without a VHC was added to assess the influence 
      of VHC presence. RESULTS: DOE study shows the presence and type of VHC are the 
      major influences on emitted dose and respirable fraction. Following the VHC 
      effect, the inhalation delay has the most significant influence on most MDI 
      performance metrics-emitted dose, respirable particle dose and fraction (aerosols 
      between 1.1 and 4.7 mum), and fine particle dose and fraction (aerosols under 
      4.7 mum). CONCLUSION: This study illustrates the use of DOE analysis to 
      effectively assess the effects of patient handling parameters (flow rate and 
      inhalation delay) on the performance of MDI drugs when used with a VHC. The 
      results of this study will inform Food and Drug Administration reviewers, the 
      pharmaceutical industry, and healthcare practitioners as to safe and effective 
      use of MDI products when used in conjunction with spacer devices.
FAU - Liu, Xiaofei
AU  - Liu X
AD  - 1 Division of Pharmaceutical Analysis, Center for Drug Evaluation and Research , 
      U.S. Food and Drug Administration, St. Louis, Missouri.
FAU - Guo, Changning
AU  - Guo C
AD  - 1 Division of Pharmaceutical Analysis, Center for Drug Evaluation and Research , 
      U.S. Food and Drug Administration, St. Louis, Missouri.
FAU - Chowdhury, Badrul
AU  - Chowdhury B
AD  - 2 Division of Pulmonary, Allergy and Rheumatology Products, Center for Drug 
      Evaluation and Research , U.S. Food and Drug Administration, Silver Spring, 
      Maryland.
FAU - Starke, Peter
AU  - Starke P
AD  - 2 Division of Pulmonary, Allergy and Rheumatology Products, Center for Drug 
      Evaluation and Research , U.S. Food and Drug Administration, Silver Spring, 
      Maryland.
FAU - Limb, Susan
AU  - Limb S
AD  - 3 Division of Pulmonary, Allergy and Rheumatology Products, Center for Drug 
      Evaluation and Research , Formally U.S. Food and Drug Administration, Silver 
      Spring, Maryland (currently Genentech).
FAU - Peri, Prasad
AU  - Peri P
AD  - 4 Office of New Drug Quality Assessment, Center for Drug Evaluation and Research 
      , Formally U.S. Food and Drug Administration, Silver Spring, Maryland (currently 
      Teva).
FAU - Schroeder, Alan
AU  - Schroeder A
AD  - 5 Office of New Drug Quality Assessment, Center for Drug Evaluation and Research 
      , U.S. Food and Drug Administration, Silver Spring, Maryland (Retired).
FAU - Doub, William
AU  - Doub W
AD  - 6 Division of Pharmaceutical Analysis, Center for Drug Evaluation and Research , 
      U.S. Food and Drug Administration, St. Louis, Missouri (Retired).
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20170828
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Aerosols)
RN  - 0 (Pharmaceutical Preparations)
MH  - Administration, Inhalation
MH  - Aerosols
MH  - Chromatography, High Pressure Liquid
MH  - *Drug Delivery Systems
MH  - Equipment Design
MH  - Humans
MH  - *Inhalation Spacers
MH  - *Metered Dose Inhalers
MH  - Particle Size
MH  - Pharmaceutical Preparations/*administration & dosage
OTO - NOTNLM
OT  - design of experiments
OT  - flow rate
OT  - in vitro
OT  - inhalation delay
OT  - metered dose inhaler
OT  - valved holding chamber
EDAT- 2017/08/29 06:00
MHDA- 2018/07/22 06:00
CRDT- 2017/08/29 06:00
PHST- 2017/08/29 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
PHST- 2017/08/29 06:00 [entrez]
AID - 10.1089/jamp.2015.1283 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2017 Dec;30(6):399-410. doi: 
      10.1089/jamp.2015.1283. Epub 2017 Aug 28.