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Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties

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Abstract

Purpose

The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product.

Methods

Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated.

Results

Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions.

Conclusions

The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

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Abbreviations

AEF:

Absorption enhancement factor

ASL:

Airway surface liquid

CFD:

Computational fluid dynamics

DAC:

Dissolution-absorption-clearance

MF:

Mometasone furoate

PK:

Pharmacokinetic

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ACKNOWLEDGMENTS AND DISCLOSURES

Dr. Geng Tian is gratefully acknowledged for his part in developing the NMT and nasal spray pump model during his time as a postdoc at Virginia Commonwealth University and Mandana Azimi for her critical review of the manuscript. This study was supported by Award U01 FD004570 and Contract HHSF223201310223C from the US FDA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US FDA.

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Authors and Affiliations

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

    Alex Rygg & P. Worth Longest

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

    Michael Hindle & P. Worth Longest

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  1. Alex Rygg
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  2. Michael Hindle
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  3. P. Worth Longest
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Correspondence to P. Worth Longest.

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Rygg, A., Hindle, M. & Longest, P.W. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties. Pharm Res 33, 909–921 (2016). https://doi.org/10.1007/s11095-015-1837-5

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