Authors: William H Doub Wallace P Adams Anna M Wokovich John C Black Meiyu Shen Lucinda F Buhse
Publish Date: 2012/07/03
Volume: 29, Issue: 11, Pages: 3122-3130
Abstract
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 volumeA 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 assemblyThe 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 assemblyUse 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 8stage 283 lpm CI flow rate configuration is recommended when using the Andersen Cascade Impactor ACI as no other assembly showed a distinct advantage
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