Development of aqueous dispersions of Coenzyme Q(10) for pulmonary delivery and the dynamics of active vibrating-mesh aerosolization

作者：Carvalho Thiago C; McCook John P; Narain Niven R; McConville Jason T^*

来源：International Journal of Pharmaceutics, 2016, 514(2): 407-419.

DOI：10.1016/j.ijpharm.2016.10.011

• Lung cancer
• Nano-dispersion
• Aerosol
• Anticancer agents

Coenzyme Q(10) (CoQ(10)) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this study was to investigate the feasibility of preparing phospholipid-stabilized dispersions of the anticancer agent for continuous pulmonary delivery using a vibrating-mesh nebulizer. We determined the physicochemical properties (drug particle size distribution in dispersion, zeta potential, surface tension, and rheology) and compared the aerosolization profiles (nebulization performance, aerodynamic drug deposition and total emitted dose) of dispersions of CoQ(10) prepared with different phospholipids. The hydrodynamic sizes of the drug particles in dispersion were primarily in the submicron range, but formulations with drug particle sizes greater than the aperture size of the nebulizer presented superior aerosolization profiles. At high shear rates, certain formulations presented increased shear-thickening behavior, which was connected to a decrease in mass and drug output over time, and with decreased aerodynamic and geometric sizes. Other formulations presented shear-thinning behavior and showed similarly high drug depositions. In this investigation, we found that dispersed formulations of CoQ(10) presented different in vitro performance for pulmonary delivery based on their rheological behavior. In conclusion, this characterization methodology provides an innovative approach to screen formulations of poorly-water soluble compounds for continuous (no clogging) active vibrating-mesh nebulization.

• 出版日期2016-12-5