The effects of freeze-drying on the stability of liposomes to jet nebulization

Egg phosphatidylcholine liposomes were freeze-dried in the presence and absence of trehalose. The lyophilized liposomes were rehydrated and aerosolized using a Pari LC jet nebulizer. The size of the aerosols generated was determined by laser diffraction, which was also used to determine the size distribution of the liposomes before lyophilization, post-rehydration, in the nebulizer post-aerosolization and those deposited in the two stages of a twin impinger. In the absence of trehalose, large liposomes and vesicle aggregates were produced on rehydration, which were rapidly reduced in size on nebulization. Liposomes with a mean size of 1 or 2.5 microm, freeze-dried with trehalose, had a mean size less than 3 microm following rehydration and exhibited enhanced stability to nebulization. Liposomes of 1 microm before freeze-drying were evenly distributed within aerosols generated by the nebulizer, whilst aerosols generated from 2.5 microm liposomes were fractionated in the twin impinger with the largest liposomes collected in the upper stage.