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In Silico Clinical Trials for Cardiovascular Disease
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Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK)
Aleksandra Vulović1, Tijana Šušteršič1, Sandra Cvijić2
1Faculty of Engineering, University of Kragujevac, Sestre Janjić 6, Kragujevac, Serbia; BioIRC, Bioengineering Research and Development Center, Prvoslava Stojanovica 6, Kragujevac, Serbia.
Summary
This study combined Computational Fluid Dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modeling to predict inhaled drug delivery. The integrated approach accurately estimated aerosol deposition and absorption for amiloride hydrochloride, improving respiratory drug delivery predictions.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Respiratory Drug Delivery Systems
- Computational Modeling and Simulation
Background:
- Accurate prediction of inhaled aerosol deposition in the respiratory tract is crucial for effective drug delivery.
- Current methods may not fully capture the complex interplay between formulation, device, and patient breathing patterns.
- Understanding drug deposition and absorption is key to optimizing dry powder inhaler (DPI) performance.
Purpose of the Study:
- To integrate Computational Fluid Dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modeling for predicting aerosolization and in vivo performance of DPIs.
- To estimate the deposition and absorption of amiloride hydrochloride using a combined CFD-PBPK approach.
- To evaluate the influence of formulation properties and physiological parameters on inhaled drug bioperformance.
Main Methods:
- Experimental determination of amiloride hydrochloride physicochemical properties.
- CFD simulations of airflow and particle deposition within a 3D model of the Aerolizer® DPI using the Discrete Phase Method (DPM).
- Development of a drug-specific PBPK model incorporating CFD-generated particle distribution data.
Main Results:
- CFD simulations provided percent emitted dose values comparable to Andersen Cascade Impactor (ACI) measurements.
- CFD predictions suggested smaller particle sizes and narrower distributions than ACI measurements indicated.
- The PBPK model successfully captured amiloride absorption patterns and demonstrated the impact of formulation on plasma concentration profiles.
Conclusions:
- The combined CFD-PBPK approach offers a powerful tool for modeling inhaled drug bioperformance.
- CFD-generated data can serve as valuable input for predicting in vivo drug deposition and absorption.
- This integrated modeling strategy enhances the understanding and optimization of respiratory drug delivery.
Keywords:
AmilorideComputational fluid dynamicsDiscrete phase modellingDry powder inhalerParticle size distributionPhysiologically-based pharmacokinetic modellingMore Related Videos
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