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CFD Assessment of Respiratory Drug Delivery Efficiency in Adults and Improvements Using Controlled Condensational Growth

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CFD Assessment of Respiratory Drug Delivery Efficiency in Adults and Improvements Using Controlled Condensational Growth Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2014 CFD Assessment of Respiratory Drug Delivery Efficiency in Adults and Improvements Using Controlled Condensational Growth Ross L. Walenga Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Biomechanical Engineering Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/3641 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Ross Lawrence Walenga 2014 All Rights Reserved CFD ASSESSMENT OF RESPIRATORY DRUG DELIVERY EFFICIENCY IN ADULTS AND IMPROVEMENTS USING CONTROLLED CONDENSATIONAL GROWTH A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by ROSS LAWRENCE WALENGA Bachelor of Science, Virginia Polytechnic Institute and State University, USA, 2000 Director: Dr. P. WORTH LONGEST Professor, Department of Mechanical and Nuclear Engineering and Department of Pharmaceutics Virginia Commonwealth University Richmond, Virginia December, 2014 ii Acknowledgment The completion of my doctorate has been a period of rapid personal and professional growth for me. At the beginning, I was able to execute a plan of action, but I had not yet developed my ability to see the big picture. Now, I find that I am able to use my natural inquisitiveness to guide my work and to confidently make meaningful decisions about the direction of my research. That does not discount the value of all the technical skill that I have developed during my time at VCU, which is significant too, but merely places it in perspective. Over the course of this process I have discovered that I love the creative and dynamic process of research with all of its unpredictability and meaningful discussion. Many people have helped tremendously during this process, for all of whom I am deeply grateful. My loving wife Amanda has been there to celebrate my accomplishments and to provide emotional support during times of difficulty. I cannot truly measure the sacrifices that she has made to ensure the successful completion of this degree, but I do know that without her I would not be where I am now. I also want to acknowledge our two beautiful daughters Abigail and Miriam, who, along with Amanda, have given me more joy than they can ever know. My advisor Dr. P. Worth Longest has made this degree possible with his generous and knowledgeable support. He told me from the start that there would be three phases of progression that I would pass through: a training phase, an application phase, and an innovation phase. I believe it is a great credit to him that I have been able to navigate these three stages and that I now have the confidence to engage in research on my own. I believe his greatest attribute iii as an advisor has been the ability to balance thoughtful support while still providing space for me to operate individually. It has always been about more than just the successful completion of a given project, as he has always had my professional development in mind. My colleagues Karl Bass, Katelyn Boone, Dr. Navvab Khajeh-Hosseini-Dalasm, Dale Farkas, Landon Holbrook, Dr. Alex Rygg, and Dr. Geng Tian have all been great partners to work with during these past few years. It was my pleasure to collaborate on a number of projects with them and to share our experiences as members of Dr. Longest’s lab. Current and former members of the VCU Department of Pharmaceutics including Dr. Michael Hindle, Dr. Ravi Behara, Dr. Renishkumar Delvadia, Dr. Laleh Golshahi, Dr. Anubhav Kaviratna, and Xiangyin Wei have all provided immense help with the in vitro experiments that are so instrumental to our research. My Ph.D. committee members were Dr. Heise, Dr. Hindle, Dr. Mossi, and Dr. Tafreshi, and I am grateful for their thoughtful comments and guidance during this process Finally, I want to acknowledge the grant funding that has made my dissertation research possible. An FDA U-award supported the characteristic tracheobronchial model and asthma constricted studies, while an NIH R01 grant supported the development of the mixer-heaters and the studies of nose-to-lung delivery in an NIV setting. iv Table of Contents ACKNOWLEDGMENT ............................................................................................................. II TABLE OF CONTENTS ........................................................................................................... IV LIST OF TABLES ................................................................................................................... VIII LIST OF FIGURES ................................................................................................................. XVI ABSTRACT ............................................................................................................................. XXV CHAPTER 1 SPECIFIC AIMS ............................................................................................. 1 CHAPTER 2 BACKGROUND .............................................................................................. 9 2.1 OBJECTIVE 1: AIRWAY AND MASK MODEL DEVELOPMENT ........................... 9 2.1.1 Characteristic Upper Airway Models ................................................................................................. 10 2.1.2 Nasal Cavity Models of Variable Constriction.................................................................................... 13 2.1.3 Existing NIV Interfaces for Aerosol Delivery ...................................................................................... 15 2.2 OBJECTIVE 2: CFD ASSESSMENT OF MDI AND DPI DELIVERY ...................... 19 2.2.1 Characterization of MDI and DPI Aerosol Delivery in the TB Airways ............................................... 20 2.2.2 Effect of Asthma Constriction on Upper and Lower Airway Aerosol Deposition ............................... 23 2.3 OBJECTIVE 3: IMPROVED AEROSOL DELIVERY DURING NIV ....................... 26 v 2.3.1 Submicrometer Particle Production for ECG and EEG delivery .......................................................... 27 2.3.2 Depositional Loss and Variability during HFT Aerosol Delivery ......................................................... 29 2.3.3 Nebulized Aerosol Delivery during NPPV ........................................................................................... 31 2.3.4 Dry Powder Aerosol Delivery during NPPV ........................................................................................ 36 2.3.5 Variability of NPPV Aerosol Delivery ................................................................................................. 40 CHAPTER 3 CHARACTERISTIC TRACHEOBRONCHIAL MODEL ...................... 42 3.1 INTRODUCTION .......................................................................................................... 42 3.2 METHODS..................................................................................................................... 44 3.3 RESULTS....................................................................................................................... 58 3.4 DISCUSSION ................................................................................................................ 67 CHAPTER 4 EFFECTS OF ASTHMA CONSTRICTION .............................................. 89 4.1 INTRODUCTION .......................................................................................................... 89 4.2 METHODS..................................................................................................................... 90 4.3 RESULTS..................................................................................................................... 103 4.4 DISCUSSION .............................................................................................................. 108 CHAPTER 5 MIXER-HEATER CONSTRUCTION AND DEVELOPMENT............ 127 5.1 INTRODUCTION ........................................................................................................ 127 5.2 METHODS................................................................................................................... 128 5.3 RESULTS..................................................................................................................... 132 5.4 DISCUSSION .............................................................................................................. 134 vi CHAPTER 6 NASAL VARIABILITY AND EEG DELIVERY .................................... 140 6.1 INTRODUCTION ........................................................................................................ 140 6.2 METHODS................................................................................................................... 142 6.3 RESULTS..................................................................................................................... 154 6.4 DISCUSSION .............................................................................................................. 162 CHAPTER 7 NEBULIZED AEROSOL DELIVERY DURING NPPV ........................ 191 7.1 INTRODUCTION .......................................................................................................
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