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Longest PW, Hindle M. Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols. Aerosol Sci Technol. 2011;45(7):884-899doi: 10.1080/02786826.2011.566592.
Longest, P. W., & Hindle, M. (2011). Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols. Aerosol science and technology : the journal of the American Association for Aerosol Research, 45(7), 884-899. https://doi.org/10.1080/02786826.2011.566592
Longest, P Worth, and Hindle, Michael. "Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols." Aerosol science and technology : the journal of the American Association for Aerosol Research vol. 45,7 (2011): 884-899. doi: https://doi.org/10.1080/02786826.2011.566592
Longest PW, Hindle M. Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols. Aerosol Sci Technol. 2011 Jan 01;45(7):884-899. doi: 10.1080/02786826.2011.566592. PMID: 21804683; PMCID: PMC3143486.
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Aerosol Sci Technol. 2011 Jan 01;45(7):884-899. doi: 10.1080/02786826.2011.566592.

Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols.

Aerosol science and technology : the journal of the American Association for Aerosol Research

P Worth Longest, Michael Hindle

Affiliations

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

PMID: 21804683 PMCID: PMC3143486 DOI: 10.1080/02786826.2011.566592

Abstract

Enhanced excipient growth is a newly proposed respiratory delivery strategy in which submicrometer or nanometer particles composed of a drug and hygroscopic excipient are delivered to the airways in order to minimize extrathoracic depositional losses and maximize lung retention. The objective of this study was to develop a validated mathematical model of aerosol size increase for hygroscopic excipients and combination excipient-drug particles and to apply this model to characterize growth under typical respiratory conditions. Compared with in vitro experiments, the droplet growth model accurately predicted the size increase of single component and combination drug and excipient particles. For typical respiratory drug delivery conditions, the model showed that droplet size increase could be effectively correlated with the product of a newly defined hygroscopic parameter and initial volume fractions of the drug and excipient in the particle. A series of growth correlations was then developed that successively included the effects of initial drug and excipient mass loadings, initial aerosol size, and aerosol number concentration. Considering EEG delivery, large diameter growth ratios (2.1-4.6) were observed for a range of hygroscopic excipients combined with both hygroscopic and non-hygroscopic drugs. These diameter growth ratios were achieved at excipient mass loadings of 50% and below and at realistic aerosol number concentrations. The developed correlations were then used for specifying the appropriate initial mass loadings of engineered insulin nanoparticles in order to achieve a predetermined size increase while maximizing drug payload and minimizing the amount of hygroscopic excipient.

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