Date of Award

2019-01-01

Degree Name

Doctor of Philosophy

Department

Environmental Science and Engineering

Advisor(s)

Vinod Kumar

Abstract

Dry powder inhalers (DPIs), used as a means for pulmonary drug delivery, typically contains a combination of an Active Pharmaceutical Ingredient (API) and significantly larger carrier particles. The micro-sized drug particles - which have a strong propensity to aggregate and a poor aerosolization performance - are mixed with significantly large carrier particles that are unable to penetrate the mouth-throat region to deagglomerate and entrain the smaller API particles in the inhaled airflow. The performance of a DPI, therefore, depends on entrainment the carrier-API combination particles and the time and thoroughness of the deagglomeration of the individual API particles from the carrier particles. Since DPI particle transport is significantly affected by particle-particle interactions, very heterogeneous particles sizes and shapes, various forces including electrostatic and Van der Waals forces, they present significant challenges to Computational Fluid Dynamics (CFD) modelers to model regional lung deposition from a DPI. In the present work, we develop a novel high fidelity CFD Discrete Element Modeling (CFD-DEM) method and sensitivity analysis for predicting the transport and deposition for DPI carrier and API particles. The proposed development will leverage exascale capable CFD-DEM and sensitivity analysis capabilities from Department of Energy (DOE) laboratories: Multiphase Flow Interface Flow Exchange (MFiX) and DAKOTA UQ software, and Trilinos portable scalable linear algebra libraries. We validate the models with available data from the literature for DPI and conduct a sensitivity analysis of various formulation properties and their effects on particle size distribution with DAKOTA. Ideal particle size can be determined based on residence time for better DPI performances and respiratory deposition. Current analysis shows that drug particles of 1-3.66 µm show a higher drug dispersion and better aerosolization behavior with carrier particles between 51-63 µm on basis of residence time.

Language

en

Provenance

Received from ProQuest

File Size

96 pages

File Format

application/pdf

Rights Holder

Antara Badhan

Download

Share

COinS