In vitro skin permeation of nicotine from proliposomes

The feasibility of proliposomes as a sustained transdermal dosage form was examined. Proliposomes containing varying amount of nicotine were prepared by a standard method using sorbitol and lecithin. The porous structure of sorbitol in the proliposomes was maintained, indicating that the majority of lecithin and nicotine is deposited within their porous matrix of the sorbitol particles. As a consequence, the flow properties of the proliposome particles was comparable to that of original sorbitol particles. Microscopic observation revealed that proliposomes are converted to liposomes almost completely within minutes following contact with water. It indicates that proliposomes may form liposomes by the sweat when they are applied on the skin under occlusive conditions in vivo. The size distribution of the reconstituted liposomes and nicotine release to pH 7.4 phosphate buffer from them were not significantly affected by the content of nicotine. The release pattern was apparently identical to the Exodus(R) patch, a commercially available transdermal nicotine formulation. We also studied in vitro permeation of nicotine across rat skin from proliposomes in a modified Keshary-Chien diffusion cell where the experimental set up simulates in vivo application of the proliposomes under an occlusive condition. The nicotine flux from proliposomes was initially retarded compared with that of nicotine powder. The flux from proliposomes appeared to remain constant throughout the experimental period compared with that of nicotine powder, indicating that nicotine may be delivered across the skin in a sustained manner at a constant rate from proliposomes. These results, therefore, indicate that sustained transdermal delivery of nicotine is feasible using proliposomal formulations if the formulations are topically applied under occlusive conditions. (C) 1997 Elsevier Science B.V.