Minimizing variability of cascade impaction measurements in inhalers and nebulizers.
The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).
Bonam
Matthew
M
Analytical Development, AstraZeneca Charnwood, Loughborough, Leicestershire, UK.
Christopher
David
D
Cipolla
David
D
Donovan
Brent
B
Goodwin
David
D
Holmes
Susan
S
Lyapustina
Svetlana
S
Mitchell
Jolyon
J
Nichols
Steve
S
Pettersson
Gunilla
G
Quale
Chris
C
Rao
Nagaraja
N
Singh
Dilraj
D
Tougas
Terrence
T
Van Oort
Mike
M
Walther
Bernd
B
Wyka
Bruce
B
D000280:Administration, Inhalation; D000336:Aerosols; D002623:Chemistry Techniques, Analytical; D004867:Equipment Design; D004868:Equipment Failure; D006801:Humans; D015233:Models, Statistical; D009330:Nebulizers and Vaporizers / Q000592:standards*; D010316:Particle Size; D011208:Powders; D011786:Quality Control; D015203:Reproducibility of Results; D019141:Respiratory System Agents / Q000008:administration & dosage* / Q000737:chemistry; D013678:Technology, Pharmaceutical
D000336:Aerosols; D011208:Powders; D019141:Respiratory System Agents