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Standardizing In Vitro Test Methods to Support Aerosol Drug Evaluation in the Clinic

Byron PR, Wei X, Delvadia RR, Longest P.

RDD Europe 2013. Volume 1, 2013: 85-92.

Abstract:

Predicting total lung deposition (TLD) or dose entering the trachea from inhalers is now claimed to be possible by conducting in vitro tests with realistic mouth-throat (MT) models using inhalation maneuvers likely to be used by patients. The literature claims that the drug aerosol escaping collection in such models (TLDin vitro) is well correlated with clinical measurements of TLDin vivo. Unfortunately, several challenges remain before standardized in vitro tests can be described, which produce results that span the lung doses seen in human subjects in the clinic. Central among these is the selection of a median flow rate versus time profile for inhalation and its lower and upper confidence limits, to represent the inhalation profiles (IPs) to be used by the clinical trial population. There are also several “realistic mouth-throat (MT) models” available with different geometries and other characteristics that leave product developers to debate whether model selection influences their TLD predictions. This paper addresses these issues and offers an approach to standardize the selection of IPs during product development. In vitro results for TLDin vitro were also compared across MT models following the use of a statistically selected, simulated inhalation profile with Salbulin™ Novolizer™ dry powder inhaler. Our results led us to ponder the validation of some of the models and discuss the topic in light of the available literature.