A novel approach to the pulmonary delivery of liposomes in dry powder form to eliminate the deleterious effects of milling

The effect of lyophilization and jet-milling on liposome integrity was investigated as a function of their ability to retain the encapsulated model drug on reconstitution of the dry products. The encapsulation efficiencies of the lyophilized and jet-milled formulations were determined at various concentrations of lactose. Lyophilization resulted in considerable leakage of the model drug at lower concentrations of lactose, and jet-milling further augmented the leakage for all the lyophilized formulations, with optimum retention obtained for formulations containing at least 10:1 molar ratio of lactose/lipid. In an attempt to overcome the deleterious effects of lyophilization and jet-milling, the feasibility of formulating phospholipid-based powders that result in spontaneous formation of liposomes in an aqueous environment has been investigated. Partitioning of three model drugs (viz., ciprofloxacin, CM3 peptide, and salbutamol sulfate) between the aqueous phase and spontaneously formed liposomes was determined in terms of encapsulation efficiency. The effects of several parameters, including lactose concentration, lipid composition, and lipid concentration on the encapsulation efficiency of these model drugs were investigated. The spontaneous formation of liposomes on dispersion of phospholipid-based powder formulations was further evidenced by freeze-fracture scanning electron microscopy. This novel approach for the delivery of liposomes in dry powder form appears promising because lyophilization is not involved and jet-milling of these powder formulations did not impact encapsulation efficiency. Jet-milled phospholipid-based powder formulations showed high encapsulation efficiencies of 96.2 +/- 1.4% for ciprofloxacin, 100% for CM3 peptide, and 45.3 +/- 3.1% for salbutamol sulfate compared with a high amount of leakage (> 50%) observed due to jet-milling of lyophilized liposome formulations encapsulating ciprofloxacin. (C) 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.