Date of Award

1-1-2013

Document Type

Masters Thesis

Degree Name

M.S.

Organizational Unit

Daniel Felix Ritchie School of Engineering and Computer Science

First Advisor

Corinne S. Lengsfeld, Ph.D.

Second Advisor

Matthew Gordon

Third Advisor

Nancy Sampson

Keywords

Aerosol optimization, Lung, Particle deposition

Abstract

The lower respiratory regions of the lung boast over 900 million alveoli with a combined 85 m2 of surface area of near direct access to the bloodstream. Within the last century the immense potential of the deep lung as a site for the delivery of drugs has begun to be exploited and today pulmonary delivery of aerosolized therapeutic is commonplace. However, the high inter- and intra-patient variability in dosing is almost completely ignored. Currently, no steps are being taken to mitigate the sources of variability beyond injection into the upper airways. This study seeks to prove that a careful selection of a particle size distribution can improve inhaler performance and reliability. In this study, lung morphometry and flow rate were considered to be the uncontrollable sources of inter- and intra-patient variability. Three populations representing different lung geometries were explored: adults aged 14-21 years old, children aged 1-9 years old and adults with severe lung remodeling. The range of flow rates considered was customized to the population based upon normal to severe asthmatic breath rates for that age group. Statistical equations predicting deposition and the MatLab function fmincon, which minimizes an objective function by the manipulation of multiple variables, was used to optimize the particle size distribution. The objective function for fmincon was the coefficient of variation (COV) and the manipulated variables were the defining parameters of the particle size distribution. This investigation demonstrated that current devices favor the healthy adult leaving critical populations such as infants and children with extremely poor deposition efficiency. The optimal particle size distributions for the adult, adult with airway remodeling and child cohorts were monodispersed with mean diameters of 3.6, 2.8 and 1.2 µm respectively. These results prove that one particle size distribution cannot be used to treat the entire population of inhaler users and more attention must be paid to selecting an appropriate size distribution.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Renee Worden

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

82 p.

Discipline

Mechanical engineering, Biomedical engineering

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