Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation.

Jelisaveta Ignjatović,Jelena Đuriš,Sandra Cvijić,Tijana Šušteršič,Aleksandar Bodić,Vladimir Dobričić,Svetlana Ibrić,Alessandra Rossi,Nenad Filipović

doi:10.3390/pharmaceutics13111831

Jelisaveta Ignjatović, Jelena Đuriš + Show 7 more

Open Access

https://doi.org/10.3390/pharmaceutics13111831

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Abstract

In vitro assessment of dry powders for inhalation (DPIs) aerodynamic performance is an inevitable test in DPI development. However, contemporary trends in drug development also implicate the use of in silico methods, e.g., computational fluid dynamics (CFD) coupled with discrete phase modeling (DPM). The aim of this study was to compare the designed CFD-DPM outcomes with the results of three in vitro methods for aerodynamic assessment of solid lipid microparticle DPIs. The model was able to simulate particle-to-wall sticking and estimate fractions of particles that stick or bounce off the inhaler’s wall; however, we observed notable differences between the in silico and in vitro results. The predicted emitted fractions (EFs) were comparable to the in vitro determined EFs, whereas the predicted fine particle fractions (FPFs) were generally lower than the corresponding in vitro values. In addition, CFD-DPM predicted higher mass median aerodynamic diameter (MMAD) in comparison to the in vitro values. The outcomes of different in vitro methods also diverged, implying that these methods are not interchangeable. Overall, our results support the utility of CFD-DPM in the DPI development, but highlight the need for additional improvements in these models to capture all the key processes influencing aerodynamic performance of specific DPIs.

Highlights

Pulmonary drug delivery, as an alternative drug administration route, gained increased interest over the past few years
The rate of deposition is determined by the particle–wall collision frequency and capture efficiency, whereas the rate of collision-induced breaking is determined by particle cohesion forces
The key outputs of the model are the emitted flow (EF), as well as total number of deposited particles and size distribution of the emitted particles

Summary

Introduction

As an alternative drug administration route, gained increased interest over the past few years. Among the various types of inhalation drug delivery devices, dry powder inhalers (DPIs) have been recognized for their benefits over, e.g., most commonly used metered dose inhalers (MDIs): (i) They do not include propellants; (ii) there is no need for coordination between device actuation and patient’s inhalation; (iii) they have improved stability; (iv) and they have better patient compliance [1,2,3]. While currently marketed DPIs include solely immediate-release products, recent research efforts have been directed towards the development of sustainedrelease DPI formulations in order to reduce dosing frequency, and increase patient compliance [4,5,6]. Pharmaceutics 2021, 13, 1831 release, these formulations possess adequate aerodynamic properties [7]. The development of inhalable SLM powders has been described in literature [7,8,9,10,11,12,13,14,15,16,17,18,19,20]; the methods/apparatuses for their aerodynamic assessment, as the most important in vitro test, have been rather diverse, e.g., multistage liquid impinger (MSLI) [7,8,9,10,11,13,15,18], Andersen cascade impactor (ACI) [8,9,12], twin stage impinger (TSI) [19], fast screening impactor (FSI) [20] and generation impactor (NGI) [20]

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