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Comparing MDI and DPI Aerosol Deposition Using In Vitro Experiments and a New Stochastic Individual Path (SIP) Model of the Conducting Airways

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Abstract

Purpose

Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles.

Methods

In vitro experiments were used to determine initial particle distribution profiles and to validate computational fluid dynamics (CFD) model results for a MDI and DPI delivering the same dose of drug in a geometry of the mouth-throat and tracheobronchial airways. The validated CFD model was then used to predict the transport and deposition of the drug using correct and incorrect inhalation profiles for each inhaler.

Results

The MDI delivered approximately two times more drug to the tracheobronchial region compared with the DPI for both correct and incorrect inhalation profiles. Errors in inhalation reduced the deposited tracheobronchial dose by approximately 30% for both inhalers. The DPI delivered the largest dose to the mouth-throat (~70%) and the MDI delivered the largest dose to the alveolar airways (~50%).

Conclusions

The developed in silico model provides new insights into the lung delivery of pharmaceutical aerosols and can be applied in future studies in combination with pharmacokinetic analysis to establish bioequivalence between devices.

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Abbreviations

B#:

bifurcation number (1 is trachea plus main bronchi)

C/P:

central to peripheral lung deposition ratio

CFC:

chlorofluorocarbon

CFD:

computational fluid dynamics

COPD:

chronic obstructive pulmonary disease

CT:

computed tomography

DE:

deposition efficiency

DF:

deposition fraction

DPI:

dry powder inhaler

ECG:

enhanced condensational growth

exp:

experiment

FR:

fraction remaining

HFA:

hydrofluoroalkane

HPLC:

high-performance liquid chromatography

LRN:

low Reynolds number

MDI:

metered dose inhaler

MMAD:

mass median aerodynamic diameter

MT:

mouth-throat

NGI:

next generation impactor

PF:

penetration fraction

QD:

quick and deep inhalation waveform

SD:

slow and deep inhalation waveform

SIP:

stochastic individual path

Ta-mean :

time of mean accelerating flow

TB:

tracheobronchial

USP:

United States Pharmacopeial

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Acknowledgments & Disclosures

This study was supported in part by a contract from the United States Food and Drug Administration (Number HHSF223201000093C). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US Food and Drug Administration.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Virginia Commonwealth University, Richmond, Virginia, USA

    P. Worth Longest, Geng Tian & Ross L. Walenga

  2. Department of Pharmaceutics, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843015, Richmond, Virginia, 23284-3015, USA

    P. Worth Longest & Michael Hindle

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  1. P. Worth Longest
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  2. Geng Tian
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  4. Michael Hindle
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Correspondence to P. Worth Longest.

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Longest, P.W., Tian, G., Walenga, R.L. et al. Comparing MDI and DPI Aerosol Deposition Using In Vitro Experiments and a New Stochastic Individual Path (SIP) Model of the Conducting Airways. Pharm Res 29, 1670–1688 (2012). https://doi.org/10.1007/s11095-012-0691-y

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