Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

Version 1 : Received: 12 October 2021 / Approved: 13 October 2021 / Online: 13 October 2021 (10:52:57 CEST)

How to cite: Miller, D.P.; Tarara, T.E.; Weers, J.G. Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations. Preprints 2021, 2021100195 (doi: 10.20944/preprints202110.0195.v1). Miller, D.P.; Tarara, T.E.; Weers, J.G. Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations. Preprints 2021, 2021100195 (doi: 10.20944/preprints202110.0195.v1).

Abstract

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

Keywords

respirable agglomerates; inhaled corticosteroids; ciclesonide; particle engineering; dry powder inhaler; extrafine; total lung dose; Alberta Idealized Throat; Idealized Child Throat

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