Geller D.E.,Aerosol Research Laboratory |
Kesser K.C.,Aerosol Research Laboratory
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2010
Background: Inhaled α1-antitrypsin (AAT) is being developed for treatment of cystic fibrosis to protect the lungs from excessive free elastase. High drug costs mandate a very efficient aerosol system to deliver a high payload to the airways. The I-neb Adaptive Aerosol Delivery (AAD) System is a portable, electronic, vibrating mesh nebulizer that delivers aerosol only during inhalation. It can be operated in conventional tidal breathing mode (TBM) or in target inhalation mode (TIM) that guides the patient to inhale deeply and slowly. The purposes of this in vitro study were to determine aerosol characteristics, device efficiency, and delivery time of AAT using the I-neb AAD System with TBM and TIM. Methods: We studied the I-neb AAD System in TBM and TIM (inspiratory time 6 or 9 sec) using a breath simulator. The loaded dose was 0.5 mL AAT (50 mg/mL). Nebulized drug captured on an inspiratory filter was reported as emitted dose. Particle size was measured by laser diffraction. Predicted lung doses were calculated based on the results of a prior scintigraphy study of the I-neb AAD System. Results: Particle size (VMD) for TBM and TIM was similar (4.4-4.8 μm). The emitted doses were very high and similar between modes (82-90% of loaded dose). Predicted lung dose of AAT (percent of loaded dose) and delivery times were: TBM 56.6% in 7.5 min; TIM-6 59.9% in 4.4 min; and TIM-9 64.5% in 2.5 min. Conclusions: The I-neb AAD System enhanced AAT delivery by inhalation-only aerosol generation and a low-residual dose. Predicted lung dose was high for both TBM and TIM, but longer inspiratory times with TIM reduced the administration time to one-third that of tidal breathing. We conclude that slow, deep, controlled inspirations using the I-neb AAD System is an efficient method to deliver AAT. © Copyright 2010, Mary Ann Liebert, Inc. 2010.
Geller D.E.,Aerosol Research Laboratory |
Weers J.,Novartis |
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2011
At present, the only approved inhaled antipseudomonal antibiotics for chronic pulmonary infections in patients with cystic fibrosis (CF) are nebulized solutions. However, prolonged administration and cleaning times, high administration frequency, and cumbersome delivery technologies with nebulizers add to the high treatment burden in this patient population. PulmoSphere™ technology is an emulsion-based spray-drying process that enables the production of light porous particle, dry-powder formulations, which exhibit improved flow and dispersion from passive dry powder inhalers. This review explores the fundamental characteristics of PulmoSphere technology, focusing on the development of a dry powder formulation of tobramycin for the treatment of chronic pulmonary Pseudomonas aeruginosa (Pa) infection in CF patients. This dry powder formulation provides substantially improved intrapulmonary deposition efficiency, faster delivery, and more convenient administration over nebulized formulations. The availability of more efficient and convenient treatment options may improve treatment compliance, and thereby therapeutic outcomes in CF. © 2011 Mary Ann Liebert, Inc.
Kalantarian P.,Aerosol Research Laboratory |
Kalantarian P.,Tehran University of Medical Sciences |
Najafabadi A.R.,Aerosol Research Laboratory |
Haririan I.,Tehran University of Medical Sciences |
And 4 more authors.
International Journal of Nanomedicine | Year: 2010
This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction. © 2010 Kalantarian et al, publisher and licensee Dove Medical Press Ltd.