Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 52, Issue -, Pages 191-205Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2013.10.016
Keywords
Pulmonary infections; Cystic fibrosis; Glass transition; Dry powder inhalers (DPIs); Aerosol dispersion performance modeling; Respiratory delivery
Categories
Funding
- UK Center of Membrane Sciences
- Graduate School Academic Year Fellowship
- Daniel R. Reedy Quality Achievement Fellowship
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The purpose of this study was to systematically design pure antibiotic drug dry powder inhalers (DPIs) for targeted antibiotic pulmonary delivery in the treatment of pulmonary infections and comprehensively correlate the physicochemical properties in the solid-state and spray-drying conditions effects on aerosol dispersion performance as dry powder inhalers (DPIs). The two rationally chosen model antibiotic drugs, tobramycin (TOB) and azithromycin (AZI), represent two different antibiotic drug classes of aminoglycosides and macrolides. respectively. The particle size distributions were narrow, unimodal, and in the microparticulate/nanoparticulate size range. The SD particles possessed relatively spherical particle morOhology, smooth surface morphology, low residual water content, and the absence of long-range molecular order. The emitted dose (ED%), fine particle fraction (FPF%) and respirable fraction (RF%) were all excellent. The MMAD values were in the inhalable range (<10 mu m) with smaller MMAD values for SD AZI powders in contrast to SD TOB powders. Positive linear correlations were observed between the aerosol dispersion performance parameter of FPF with increasing spray-drying pump rates and also with the difference between thermal parameters expressed as T-g - T-o (i.e. the difference between the glass transition temperature and outlet temperature) for SD AZI powders. The aerosol dispersion performance for SD TOB appeared to be influenced by its high water vapor sorption behavior (hygroscopicity) and pump rates or T-o. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system. (C) 2013 Elsevier B.V. All rights reserved.
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