Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Abstract

Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/ nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan ® software and were determined to be 600 nm to 1.2 µm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler ® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 µm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved. Dovepresssubmit your manuscript | www.dovepress.com

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

“…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).…”

“…Images were captured at several magnifications using similar conditions previously reported by the authors. (Meenach et al, 2013). …”

“…Inhalation aerosol delivery dates back to ancient times (Hickey and Mansour, 2009; Patton and Byron, 2007) and aerosol formulations have been investigated for many pulmonary diseases including lung infections, cystic fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer (Arnold et al, 2007; Cartiera et al, 2010; Meenach et al, 2012; Meenach et al, 2013; Watts et al, 2008; Yang et al, 2009). Nebulizers, pressurized metered dose inhalers (pMDIs), soft-mist inhalers (SMIs), and dry powder inhalers (DPIs) are the various types of commercially available pulmonary drug delivery systems currently used in the treatment of human pulmonary diseases and have been described in detail (Hickey and Mansour, 2009).…”

“…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).…”

“…Also, for certain formulations, the relatively low clearance rate in the bronchioalveolar region may also allow for longer residence times (Carvalho et al, 2011). We have recently reported on the successful design and optimization of the novel DPI nanomedicine carrier platform consisting of DPPC/DPPE-PEG with varying PEG chain length and excellent aerosol dispersion performance as aerosolized dry powders (Meenach et al, 2013). …”