title: Measurement of drug in small particles from aqueous nasal sprays by Andersen Cascade Impactor.
abstract: OBJECTIVE
  To determine if cascade impactor (CI) measurement of drug in small particles from aqueous nasal sprays, described in FDA's 2003 draft Nasal Bioavailability/Bioequivalence Guidance, can be optimized to reduce measurement variability. To examine the influence of flow rate configurations and number of impactor stages on CI deposition and explore the importance of inlet volume.
  
  
  METHODS
  A total of eight assemblies and manual vs. automatic actuation were tested for deposition on the sum of all stages of the CI, and for Group 2 total drug mass per the Guidance. Mean deposition and variance about the mean were determined for each assembly.
  
  
  RESULTS
  The path length for a spherical 1 l inlet was too short to allow adequate aerosol formation. Data variance was reduced by a factor of two or more by using an automatic actuator relative to manual actuation. Impactor assembly modification did not improve variance over the standard assembly.
  
  
  CONCLUSIONS
  Use of a spherical inlet (≥ 2 l volume) and automatic actuation are recommended for comparative measurements of drug in small particles arising from aqueous nasal sprays. The standard (8-stage) 28.3 lpm CI flow rate configuration is recommended when using the Andersen Cascade Impactor (ACI), as no other assembly showed a distinct advantage.
authors: Division of Pharmaceutical Analysis, Food and Drug Administration CDER, OPS, St. Louis, Missouri, USA. william.doub@fda.hhs.gov
authors: William H
authors: WH
authors: Doub
authors: Wallace P
authors: WP
authors: Adams
authors: Anna M
authors: AM
authors: Wokovich
authors: John C
authors: JC
authors: Black
authors: Meiyu
authors: M
authors: Shen
authors: Lucinda F
authors: LF
authors: Buhse
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000737:chemistry*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation*; D004867:Equipment Design / Q000295:instrumentation*; D036501:Metered Dose Inhalers; D059085:Nasal Sprays; D010316:Particle Size; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry*; D019141:Respiratory System Agents / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000336:Aerosols; D059085:Nasal Sprays; D019999:Pharmaceutical Solutions; D019141:Respiratory System Agents