In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

Abstract

The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CIgenerated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

Powder Particles and Technologies for Medicine Delivery to the Respiratory System: Challenges and Opportunities

“…4, it is difficult to unequivocally indicate the optimum particle size, in particular considering intersubject variability in inhalation flow dynamics and airway geometry where both can be additionally altered in lung disease. Mitchell J. et al (2007) additionally pointed out that the clinical response (the real in-vivo effect) will depend not only on the actual deposition of drug particles but also on the drug potency and the severity of lung disorder. These authors also discussed other limitations of application of the results of aerodynamic particle sizing to predict the regional aerosol deposition in the respiratory system.…”

“…Although some additional technical improvements of cascade impactors have been proposed such as a more realistic mouth-throat model instead of the standard inlet (Copley M. et al, 2011), the problem of a direct conversion of the measured particle size to the real in-vivo drug delivery and efficacy still remains unsolved (Clark A.R. and Borgström L., 2002;Mitchell J. et al, 2007).…”

Assessing New Technologies in Aerosol Medicine: Strengths and Limitations

“…95 During cascade impaction characterization, the aerosol is suctioned into the impactor and classified according to its size while it travels through different stages. 96 Particlesize distribution is calculated according to pharmacopeial recommendations after biochemical determination of the amount of drug present at each stage. 97,98 Although we always stress the importance of size as a major determining factor in lung deposition, the use of the appropriate breathing technique can result in high intrapulmonary deposition of larger particles.…”

In Vitro–In Vivo Correlation: Shades on Some Non-Conventional Dosage Forms

“…It is assumed that cascade impactor deposition data may correlate to the drug deposition in lungs (12). Due to the complexity of this route of application, a comparison of aerodynamic particle size distribution (APSD) profiles may not confirm bioequivalence.…”