Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

Abstract

Abstract:In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug -cyclosporine A -for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero-3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters.

Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer

“…Using similar conditions previously reported by the authors (Li and Mansour, 2011; Meenach et al, 2013; Wu et al, 2013a; Wu et al, 2013b), 1 – 3 mg of powder was weighed into hermetic anodized aluminum T-Zero ® DSC pans and were sealed hermetically sealed with the T-Zero ® hermetic sealer. UHP dry nitrogen gas was used as the purging gas at 50 mL/min.…”

“…95 mole % DPPC to 5 mole % DPPE-PEG) with different amounts of paclitaxel (PTX) ranging from 5 to 75 mole% paclitaxel to total DPPC/DPPE-PEG in methanol to form dilute concentration feed solutions of 0.1% w/v. Based on our previous work (Li et al, 2011; Li and Mansour, 2011; Meenach et al, 2013; Wu et al, 2013a; Wu et al, 2013b), the following spray-drying conditions were used: atomization gas flow rate of 600 L/h, aspiration rate of 35 m 3 /h, inlet temperature of 150 °C (which represents the primary drying step), and pump rate of 30 mL/min (High P). Table I shows the various formulated particle systems and their corresponding PTX and DPPC/DPPE-PEG amounts and types and outlet temperatures (which represent the secondary drying process temperatures).…”

“…(Li and Mansour, 2011; Meenach et al, 2013; Wu et al, 2013a; Wu et al, 2013b) The measurements were performed with a 737 KF Coulometer coupled with 703 Ti Stand (Metrohm Ltd., Antwerp, Belgium). Approximately 5 mg of powder was dissolved in a known volume of chloroform.…”

“…These are similar conditions, as previously reported by the authors. (Li and Mansour, 2011; Meenach et al, 2013; Wu et al, 2013a; Wu et al, 2013b). …”

“…This includes the ability to design the particle size and amount of drug loaded into the system, improved chemical stability relative to liquid aerosols, and improved long-term stability during pharmaceutical storage timescales (Hickey and Mansour, 2008; Mansour et al, 2009; Sung et al, 2007). In this study, dry powder nanoparticle/microparticle formulations were designed via organic solution advanced spray drying in closed-mode which has been optimized by our group for the delivery of therapeutics to treat various lung diseases (Li et al, 2011; Li and Mansour, 2011; Meenach et al, 2013; Wu et al, 2013a; Wu et al, 2013b). Spray drying is an advanced high-throughput pharmaceutical manufacturing particle engineering process which can design and efficiently produce respirable particles in the solid-state (Hickey and Mansour, 2008; Kikuchi et al, 1991; Mansour et al, 2009; Mansour et al, 2011).…”