title: Improved quality control metrics for cascade impaction measurements of orally inhaled drug products (OIPs).
abstract: This study of aerodynamic mass-weighted particle size distribution (APSD) data from orally inhaled products (OIPs) investigated whether a set of simpler (than currently used) metrics may be adequate to detect changes in APSD for quality control (QC) purposes. A range of OIPs was examined, and correlations between mass median aerodynamic diameter and the ratio of large particle mass (LPM) to small particle mass (SPM) were calculated. For an Andersen cascade impactor, the LPM combines the mass associated with particle sizes from impactor stage 1 to a product-specific boundary size; SPM combines the mass of particles from that boundary through to terminal filter. The LPM-SPM boundary should be chosen during development based on the full-resolution impactor results so as to maximize the sensitivity of the LPM/SPM ratio to meaningful changes in quality. The LPM/SPM ratio along with the impactor-sized mass (ISM) are by themselves sufficient to detect changes in central tendency and area under the APSD curve, which are key in vitro quality attributes for OIPs. Compared to stage groupings, this two-metric approach provides better intrinsic precision, in part due to having adequate mass and consequently better ability to detect changes in APSD and ISM, suggesting that this approach should be a preferred QC tool. Another advantage is the possibility to obtain these metrics from the abbreviated impactor measurements (AIM) rather than from full-resolution multistage impactors. Although the boundary is product specific, the testing could be accomplished with a basic AIM system which can meet the needs of most or all OIPs.
authors.affiliation: CMC Development, Boehringer Ingelheim, Ridgefield, Connecticut, USA.
authors.forename: Terrence P
authors.initials: TP
authors.lastname: Tougas
authors.forename: David
authors.initials: D
authors.lastname: Christopher
authors.forename: Jolyon P
authors.initials: JP
authors.lastname: Mitchell
authors.forename: Helen
authors.initials: H
authors.lastname: Strickland
authors.forename: Bruce
authors.initials: B
authors.lastname: Wyka
authors.forename: Mike
authors.initials: M
authors.lastname: Van Oort
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lyapustina
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000592:standards*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011786:Quality Control; D012044:Regression Analysis; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000592:standards*
chemical_list: D000336:Aerosols