Physical stability and aerosol properties of liposomes delivered using an air-jet nebulizer and a novel micropump device with large mesh apertures

Abstract

The aerosol properties of liposomes and their physical stability to aerosolization were evaluated using an air-jet nebulizer (Pari LC Plus) and a customized large aperture vibrating-mesh nebulizer (Aeroneb Pro-8microm). Soya phosphatidylcholine: cholesterol (1:1 mole ratio) multilamellar liposomes (MLVs) entrapping salbutamol sulfate were nebulized directly, or after being reduced in size by extrusion through 1 or 0.4microm polycarbonate membrane filters. MLVs were very unstable to jet nebulization and stability was not markedly enhanced when vesicles were extruded before nebulization, such that drug losses from delivered liposomes using the Pari nebulizer were up to 88% (i.e. only 12% retained in liposomes). The Aeroneb Pro-8microm nebulizer was less disruptive to liposomes, completed nebulization in a much shorter time, and produced greater mass output rate than the Pari nebulizer. However, aerosol droplets were larger, total drug and mass outputs were lower and aerosolization performance was dependent on formulation. Vibrating-mesh nebulization was less disruptive to liposomes extruded through the 1microm membranes compared with the non-extruded MLVs, so that the retained entrapment of the drug in the nebulized vesicles was 56% and 37%, respectively. However, extrusion of liposomes to 0.4microm resulted in reduced stability of liposomes to vibrating-mesh nebulization (retained entrapment=41%) which was attributed to the reduced liposome lamellarity and subsequent reduced resistance to nebulization-induced shearing. This study has shown that vibrating-mesh nebulization using the customized large aperture mesh nebulizer (Aeroneb Pro-8microm) had a less disruptive effect on liposomes and produced a higher output rate compared with the Pari LC Plus air-jet nebulizer. On the other hand, the air-jet nebulizer produced higher total mass and drug outputs and smaller aerosol droplets.