Inhaled aerosols as carriers of pulmonary medicines and the limitations of in vitro – in vivo correlation (IVIVC) methods

Pulmonary drug delivery (PDD) involves flow and deposition of aerosol particles acting as carriers of drugs delivered onto the surface of the airways. As a direct consequence, optimal PDD requires controlling of drug aerosolization processes and deep understanding of multiphase flows in complex geometry of the airways including aerosol particle dynamics during the transient inhalation cycles. A chemical engineering-based approache can be effectively used to analyze these processes and help in designing optimized drug formulations and more effective drug delivery devices (inhalers). One of prerequisites of improved PDD is the knowledge of in vivo–in vitro correlation (IVIVC) for inhaled drugs that would allow establishment of the relationships between aerosol quality determined using ex vivo methods (such as determination of particle size, deposition in reconstructed anatomical structures, pharmacokinetics/pharmacodynamics using in vitro cellular systems, or in silico modeling of aerosol dynamics) in connection to the clinical effects. This manuscript discusses the challenges of the IVIVC analyses for aerosol delivery systems. The primary focus is given to the physical and physicochemical constraints in the PDD that can be effectively described and investigated using engineering approaches.