Phospholipid/Drug Interactions in Liposomes Studied by Rheological Properties of Monolayers

In order to obtain a good knowledge of the pharmaceutical form, we sought to localize the antiacneic drug RU 58841 in liposomes. The mixed drug/phospholipid monolayer obtained by spreading phospholipids at the air/aqueous surface of drug solutions was studied using the film balance technique to clarify the organization of the film respect to its composition and state of compression. A rheological approach based on Maxwell's model was found to be useful to discriminate between the influence of each constituent in the monolayer. From the study of the isotherms and the rheological behavior of mixed monolayers at low surface pressures it was deduced that the drug could be localized between the phospholipids polar headgroups. In the opposite case, at high surface pressures, the drug molecule was believed to be trapped in the hydrophobic part of the phospholipidic layer and behave like an insoluble one. The surface film formation kinetics of drug-loaded liposomes is faster than the corresponding kinetics of unloaded liposomes.