Development and characterization of phospholipid-stabilized submicron aqueous dispersions of coenzyme Q₁₀ presenting continuous vibrating-mesh nebulization performance

Abstract

Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. The aim of this research was to develop a suitable formulation for pulmonary delivery of this anticancer agent. An appropriate selection of excipients (phospholipids) and a suitable device (Aeroneb Pro® vibrating-mesh nebulizer) were selected initially after reviewing the literature. After characterization of the bulk drug, a feasible manufacturing process was selected to obtain small particle size dispersions of CoQ₁₀. Following selection of an appropriate process, the parameters affecting drug particle size were studied. Using LD and gravimetrical analysis, nebulization was evaluated to assess the performance of the inhalation system triad: drug–excipients–device. CoQ₁₀ powder studied was crystalline with a melting point approximately at 51 °C and with a particle size of 30 µm. Microfluidization was found to be a suitable method to prepare submicron drug particles in aqueous dispersions. Increasing microfluidization processing to more than 50 passes did not provide further particle downsizing for both soya phosphatidylcholine (lecithin) and dipalmitoyl phosphatidylcholine (DPPC) dispersions of CoQ₁₀, presenting Z-average values of approximately 130 and 70 nm, respectively. Nebulization performance of lecithin-stabilized CoQ₁₀ dispersions varied according to number of passes in the microfluidizer. Formulations processed with 10 passes presented steadier nebulization over time and different rheological behavior compared to those processed with 30 or 50 passes. In conclusion, aqueous dispersions of CoQ₁₀ were adequately produced using a microfluidizer with characteristics that were suitable for pulmonary delivery with an Aeroneb Pro® nebulizer. Furthermore, the rheology of these dispersions appeared to play a significant role in the aerosol generation from the active vibrating-mesh nebulizer used.

• Anticancer agents
• formulation development
• inhalation delivery
• nebulizers
• rheology
• suspensions