Advanced design and development of nanoparticle/microparticle dual-drug combination lactose carrier-free dry powder inhalation aerosols
Author
Muralidharan, PriyaMallory, Evan K.
Malapit, Monica
Phan, Hanna
Ledford, Julie G.
Hayes, Don
Mansour, Heidi M.
Affiliation
Univ Arizona, Coll PharmUniv Arizona, Dept Cellular & Mol Med, Coll Med
Univ Arizona, Dept Med, Div Translat & Regenerat Med, Coll Med
Univ Arizona, BIO5 Res Inst
Univ Arizona, Inst Environm
Issue Date
2020
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Royal Society of Chemistry (RSC)Citation
Muralidharan, P., Mallory, E. K., Malapit, M., Phan, H., Ledford, J. G., Hayes, D., & Mansour, H. M. (2020). Advanced design and development of nanoparticle/microparticle dual-drug combination lactose carrier-free dry powder inhalation aerosols. RSC advances, 10(68), 41846-41856.Journal
RSC AdvancesRights
This journal is © The Royal Society of Chemistry 2020. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Rationale: lactose is the only FDA-approved carrier for dry powder inhaler (DPI) formulations in the US. Lactose carrier-based DPI products are contraindicated in patients with a known lactose allergy. Hence, inhaler formulations without lactose will benefit lactose allergic asthmatics. Objectives: to rationally design and develop lactose carrier-free dry powder inhaler formulations of fluticasone propionate and salmeterol xinafoate that will benefit people with known lactose allergy. The study also aims at improving the aerosol deposition of the dry powder formulation through advanced particle engineering design technologies to create inhalable powders consisting of nanoparticles/microparticles. Methods: advanced DPI nanoparticle/microparticle formulations were designed, developed and optimized using organic solution advanced closed-mode spray drying. The co-spray dried (co-SD) powders were comprehensively characterized in solid-state and in vitro comparative analysis of the aerodynamic performance of these molecularly mixed formulations was conducted with the marketed formulation of Advair (R) Diskus (R) interactive physical mixture. Measurements and main results: comprehensive solid-state physicochemical characterization of the powders showed that the engineered co-SD particles were small and spherical within the size range of 450 nm to 7.25 mu m. Improved fine particle fraction and lower mass median aerodynamic diameter were achieved by these DPI nanoparticles/microparticles. Conclusions: this study has successfully produced a lactose-free dry powder formulation containing fluticasone propionate and salmeterol xinafoate with mannitol as excipient engineered as inhalable DPI nanoparticles/microparticles by advanced spray drying. Further, co-spray drying with mannitol and using Handihaler (R) device can generate higher fine particle mass of fluticasone/salmeterol. Mannitol, a mucolytic agent and aerosol performance enhancer, is a suitable excipient that can enhance aerosol dispersion of DPIs.Note
Open access journalEISSN
2046-2069Version
Final published versionSponsors
National Institute of Allergy and Infectious Diseasesae974a485f413a2113503eed53cd6c53
10.1039/d0ra07203f
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Except where otherwise noted, this item's license is described as This journal is © The Royal Society of Chemistry 2020. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.