Search

Prediction of local exposure following inhalation of a locally acting pulmonary drug is central to the successful development of novel inhaled medicines, as well as generic equivalents. This work provides a comprehensive review of the state of the art with respect to multiscale computer models designed to provide a mechanistic prediction of local and systemic drug exposure following inhalation. The availability and quality of underpinning in vivo and in vitro data informing the computer based models is also considered. Mechanistic modelling of local exposure has the potential to speed up and improve the chances of successful inhaled API and product development. Although there are examples in the literature where this type of modelling has been used to understand and explain local and systemic exposure, there are two main barriers to more widespread use. There is a lack of generally recognised commercially available computational models that incorporate mechanistic modelling of regional lung particle deposition and drug disposition processes to simulate free tissue drug concentration. There is also a need for physiologically relevant, good quality experimental data to inform such modelling. For example, there are no standardized experimental methods to characterize the dissolution of solid drug in the lungs or measure airway permeability. Hence, the successful application of mechanistic computer models to understand local exposure after inhalation and support product development and regulatory applications hinges on: (i) establishing reliable, bio-relevant means to acquire experimental data, and (ii) developing proven mechanistic computer models that combine: a mechanistic model of aerosol deposition and post-deposition processes in physiologically-based pharmacokinetic models that predict free local tissue concentrations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We present a novel method for characterizing in near real-time the aerodynamic particle size distributions from pharmaceutical inhalers. The proposed method is based on direct imaging of airborne particles followed by a particle-by-particle measurement of settling velocities using image analysis and particle tracking algorithms. Due to the simplicity of the principle of operation, this method has the potential of circumventing potential biases of current real-time particle analyzers (e.g. Time of Flight analysis), while offering a cost effective solution. The simple device can also be constructed in laboratory settings from off-the-shelf materials for research purposes. To demonstrate the feasibility and robustness of the measurement technique, we have conducted benchmark experiments whereby aerodynamic particle size distributions are obtained from several commercially-available dry powder inhalers (DPIs). Our measurements yield size distributions (i.e. MMAD and GSD) that are closely in line with those obtained from Time of Flight analysis and cascade impactors suggesting that our imaging-based method may embody an attractive methodology for rapid inhaler testing and characterization. In a final step, we discuss some of the ongoing limitations of the current prototype and conceivable routes for improving the technique., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: A new inhaler (Medspray) for pulmonary drug delivery based on the principle of Rayleigh break-up has been tested with three different spray nozzles (1.5; 2.0 and 2.5 mum) using aqueous 0.1% (w/w) salbutamol and 0.9% (w/w) sodium chloride solutions., Materials and Methods: Particle size distributions in the aerosol were measured with the principles of time of flight (APS) and laser diffraction (LDA)., Results: The Medspray inhaler exhibits a highly constant droplet size distribution in the aerosol during dose emission. Droplets on the basis of Rayleigh break-up theory are monodisperse, but due to some coalescence the aerosols from the Medspray inhaler are slightly polydisperse. Mass median aerodynamic diameters at 60 l.min(-1) from APS are 1.42; 1.32 and 1.27 times the theoretical droplet diameters (TD's) and median laser diffraction diameters are 1.29; 1.14 and 1.05 times TD for 1.5; 2.0 and 2.5 mum nozzles (TD: 2.84; 3.78 and 4.73 mum respectively)., Conclusions: The narrow particle size distribution in the aerosol from the Medspray is highly reproducible for the range of flow rates from 30 to 60 l.min(-1). The mass median aerodynamic droplet diameter can be well controlled within the size range from 4 to 6 mum at 60 l.min(-1).