Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried microparticulate/nanoparticulate antibiotic dry powders of tobramycin and azithromycin for pulmonary inhalation aerosol delivery.
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 morphology, 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 μm) 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 Tg-To (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 To. Aerosol dispersion performance of SD powders were distinct for both antibiotic drug aerosol systems and also between different pump rates for each system.
University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences-Drug Development Division, 789 S. Limestone St., Lexington, KY 40536-0596, USA.
Xiaojian
X
Li
GlaxoSmithKline, Analytical Sciences, Product Development, King of Prussia, PA 19406, USA.
Frederick G
FG
Vogt
The Ohio State University, College of Medicine, Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Columbus, OH 43205, USA; The Ohio State University, College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH 43205, USA.
Don
D
Hayes
University of Arizona-Tucson, College of Pharmacy, Skaggs Pharmaceutical Sciences Center, 1703 E. Mabel St., Tucson, AZ 85721, USA. Electronic address: mansour@pharmacy.arizona.edu.
Heidi M
HM
Mansour
D000280:Administration, Inhalation; D000336:Aerosols; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D017963:Azithromycin / Q000737:chemistry*; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D000432:Methanol / Q000737:chemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D033362:Powder Diffraction; D011208:Powders; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical; D014031:Tobramycin / Q000737:chemistry*; D014961:X-Ray Diffraction
D000336:Aerosols; D000900:Anti-Bacterial Agents; D011208:Powders; D012996:Solutions; D017963:Azithromycin; D014031:Tobramycin; D000432:Methanol
Aerosol dispersion performance modeling; Cystic fibrosis; Dry powder inhalers (DPIs); Glass transition; Pulmonary infections; Respiratory delivery