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Predictive In Vitro Dissolution Methods for Orally Inhaled Drug Products

Shur J, Price R.

RDD Asia 2016. Volume , 2016: 121-130.

Abstract:

New tools are required to enable the development of predictive understanding of drug deposition and dosimetry in the area of inhaled biopharmaceutics. Moreover, there is a growing need to understand the extent and rate of drug absorption, through the measurement of the rate of dissolution of aerosolized particles. New approaches have been developed utilizing air-liquid interface (ALI) cell culture models that have been incorporated into an inertial impactor and a non-cell culture based aerosol collection system to aid measurement of the dissolution of the aerosol dose (UniDose). Snapwell-grown inserts of a Calu-3 ALI cell model were successfully integrated to develop a cell-compatible next generation impactor (cNGI) deposition system enabling the administration of aerosolized drug on to Calu-3 cell monolayers. The system was used to investigate the dissolution and permeation of budesonide aerosolized from a commercial Pulmicort® pMDI. The dissolution half-life of commercially available formulations of inhaled corticosteroids assessed using UniDose correlated with in vivo mean absorption times, reported in the literature. This study has demonstrated the application of the UniDose approach to improve the discriminatory capability of aerosol dissolution testing, and may facilitate the link between dissolution and systemic absorption of molecules in the airways.