Design Op miza on of Dry Powder Inhalers for Weak Dependence on HumanCondi ons

Introduc on

According toWorldHealthOrganiza on (WHO), there are over 235million people suffering fromasthmaand Chronic Obstruc ve Pulmonary Disease (COPD). Nearly all of those pa ents rely on inhalers fortreatment. In recent years, dry powder inhalers (DPIs) are becoming increasingly popular due to thefact that they do not require pa ents to coordinate between breathing and release of medicine. Drypowder inhalers (DPIs) achieve this advantage by allowing the pa ents to inhale through the medicineinstead of spraying the medicine in mouth.

AlthoughDPIs performbe er than other inhalers, varia on in pa ent to pa ent breathing pa ern spoilstheir performance. A younger personmay inhalemore air than an older one and varia ons of this naturehave been found to effect the func onality of inhalers [3]. A person using inhaler may belong to any agegroup; thus, requiring inhaler to performconsistently over awide range of pa ents. Another reason thatcontributes in inconsistent performance of DPIs is insufficient accuracy in design of inhalers. Accuracyof design process of DPIs is compromised due to unavailability of accurate force models in literature forpar cles in a mul phase flow. Inaccurate mathema cal descrip on of forces on drug par cle is a bigproblem in designing a rather consistent dry powder inhaler. If an accurate modeling of forces ac ngon par cles in a mul phase flow can be achieved, design of an inhaler that performs consistently for awide variety of pa ents is just another step.

This research intends to develop more accurate force models for par cles and employ computer simu-la on to study the drug par cle dynamics in complex inhaler geometry. Main outcome of the researchwill be an improved design with weak dependence on human condi ons so that drug delivery efficiencycan be improved. In order to op mize inhaler design, a number of force models for drug par cles willbe developed and tested to accurately describe transport of drug par cle in inhaler geometry.

Methodology

When designing inhalers, one and only aim is to op mize its drug delivery efficiency for wide rangeof pa ents. Dynamics of drug par cle in a complex geometry like inhaler is governed by many differ-ent physical processes. The problem to be solved involves a complex geometry; therefore, it is notreasonable to expect an analy cal solu on to the problem. The solu on of the flow in inhalers willbe computed numerically and will be used to study transport of drug par cles. The methodology toop mize the inhaler design is divided into following steps:

1. Modeling the inhaler geometry to obtain the flow solu on

2. Par cle tracking with developed force models

3. Experimental verifica on

4. Inhaler design op miza on.

I have already developed a numerical framework to solve incompressible flow in mymaster studies andit will be used to obtain flow field in poten al inhaler design. In order to accurately predict the mo-on of drug par cle, modeling of complex forces experienced by the par cle is needed. Force models

given in available literature [1, 4] can be a good start. With the force models, par cles can be trackedusing Lagrangian par cle tracking. Results obtained numerically will be compared with experiments toes mate accuracy of the developed forcemodels. Depending on the amount and the nature of discrep-ancies, models will be updated to predict be er results. Once accurate modeling of forces experiencedby the drug par cle is completed, a number of inhaler geometries will be inves gated for their abilityto perform consistently for varying breathing pa erns.

Required Resources

Important resources needed to carry out proposed research are briefly discussed here.

1. When a pa ent inhales through the medicine, its proper es can change. Size and proper es ofinhaled medicine are required parameters for this research; therefore, a strong collabora on with de-partment of medicine is needed for this research to progress smoothly.

2. Lagrangian par cle tracking provides the benefit of assigning par cles to each cpu core and trackthem independently [2]. Thus, facility of parallel computa on is essen al to carry out this research.

3. Force models developed in this research require experimental verifica on. Experimental techniquesuch as par cle image velocimetry (PIV) is needed to relate the simula on results with experiments.

Expected Outcomes

Proposed research intends to op mize the performance of dry powder inhalers. Moreover, it requiresdevelopment of accurate force models so that a realis c simula on of mul phase flow in inhalers canbe achieved. Following outcomes are expected from proposed research.

1. Development of sophis cated force models for solid par cles in any mul phase flow so that simula-on accuracy can be improved.

2. Design of an op mized inhaler geometry with consistent performance for a wider variety of pa ents.

Relevant Research Experience

I have gained decent experience in fluid mechanics through my research projects in bachelor and mas-ter degrees. In my master thesis I worked on the fundamental research of the flow-moving surface

interac on. In order to numerically study the problem, I developed a finite difference incompressibleflow solver for two-dimensional flows. I am very proud that some new insights have been obtainedand this work has been submi ed to Physics of Fluid (revision resubmi ed already a er the first roundreview). The code I developed employed RANS to simulate turbulent flows. Recently, I have appendedthe code with LES/RANS hybrid method to solve turbulent flow problemsmore accurately. My bachelordisserta on was to design a high subsonic reconnaissance UAV with the range of two hundred kilome-ters. Main responsibili es of my group (one other member) were to propose a conceptual design of theUAV, aerodynamically op mize the design using CFD, perform pay-load analysis and share the designinforma on with the group performing structural op miza on. A commercial CFD so ware was usedto model the proposed design, study its performance and iden fy improvements.

I am aware of the level of persistence and resilience required for pursuing this research and I am confi-dent that I am adequately equipped to contribute to the proposed area of research.

References

[1] S Balachandar and John K Eaton. Turbulent dispersed mul phase flow. Annual Review of FluidMechanics, 42:111–133, 2010.

[2] Douglas Barker, Jonathan Lifflander, Anshu Arya, and Yuanhui Zhang. A parallel algorithm for 3dpar cle tracking and lagrangian trajectory reconstruc on. Measurement Science and Technology,23(2):025301, 2012.

[3] Ma hew S Coates, Hak-Kim Chan, David F Fletcher, and Judy A Raper. Effect of design on the per-formance of a dry powder inhaler using computa onal fluid dynamics. part 2: Air inlet size. Journalof pharmaceu cal sciences, 95(6):1382–1392, 2006.

[4] Abhijit Guha. Transport and deposi on of par cles in turbulent and laminar flow. Annu. Rev. FluidMech., 40:311–341, 2008.