Evaluation of Abbreviated Impactor Measurements (AIM) and Efficient Data Analysis (EDA) for Dry Powder Inhalers (DPIs) Against the Full-Resolution Next Generation Impactor (NGI).
The full-resolution next generation impactor (NGI) and three abbreviated impactor systems were used to obtain the apparent aerodynamic particle size distribution (APSD) and other quality measures for marketed dry powder inhalers (DPIs) using the compendial method and efficient data analysis (EDA). APSD for the active pharmaceutical ingredient (API) in Spiriva®Handihaler®, Foradil®Aerolizer®, and Relenza®Diskhaler®was obtained using a full-resolution NGI at 39, 60, and 90 L/min, respectively. Two reduced NGI (rNGI) configurations, the filter-only configuration (rNGI-f) and the modified-cup configuration (rNGI-mc), and the fast-screening impactor (FSI) with appropriate inserts to provide a 5-μm cut size were evaluated. The fine particle dose (FPD) obtained using the FSI for Spiriva was statistically similar to that obtained using the full NGI. However, the FPD for both Foradil and Relenza obtained using the FSI was significantly different from that obtained using the full NGI. Despite this, no significant differences were observed for the fine particle fraction (FPF) obtained using the FSI relative to that obtained from the full NGI for any of the DPIs. The use of abbreviated impactor systems appears promising with good agreement observed with the full-resolution NGI, except for small differences observed for the rNGI-mc configuration. These small differences may be product- and/or flow rate-specific, and further evaluation will be required to resolve these differences.
Division of Pharmaceutical Analysis, Food and Drug Administration, 645 S Newstead Avenue, Saint Louis, Missouri, 63110, USA.
Megha
M
Mohan
Office of Pharmaceutical Quality, Immediate Office, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Sau
S
Lee
Division of Pharmaceutical Analysis, Food and Drug Administration, 645 S Newstead Avenue, Saint Louis, Missouri, 63110, USA. changning.guo@fda.hhs.gov.
Changning
C
Guo
Office of New Drug Quality Assurance, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.|Teva Pharmaceutical Industries, 41 Moore Road, Frazer, Pennsylvania, 19355, USA.
S Prasad
SP
Peri
Division of Pharmaceutical Analysis, Food and Drug Administration, 645 S Newstead Avenue, Saint Louis, Missouri, 63110, USA.
William H
WH
Doub
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry / Q000494:pharmacology; D058995:Dry Powder Inhalers / Q000379:methods*; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008422:Materials Testing / Q000379:methods; D036501:Metered Dose Inhalers; D010316:Particle Size; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000737:chemistry; D053243:Zanamivir / Q000008:administration & dosage / Q000737:chemistry
D000336:Aerosols; D019141:Respiratory System Agents; D053243:Zanamivir; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
abbreviated impactor measurement; efficient data analysis; fine particle dose; fine particle fraction; next generation impactor