Interaction of Oxicam NSAIDs with lipid monolayer: Anomalous dependence on drug concentration

Surface pressure (π) versus specific molecular area (A) isotherms of Langmuir monolayers of dimyristoylphosphatidylcholine (DMPC) lipid on pure water were studied in pristine form and in presence of three non-steroidal anti-inflammatory drugs, meloxicam (MX), piroxicam (PX) and tenoxicam (TX) in the subphase. Data were taken at three drug/lipid (D/L) ratios of 0.026, 0.05, and 0.1. Integration of drug to the lipid monolayer was measured by the increase in A (ΔA) of DMPC monolayer due to the presence of drugs. All three drugs could be integrated in the monolayer resulting in a positive value of ΔA for D/L ratio of 0.026. Above this D/L value, there is an anomalous, monotonic decrease in ΔA for MX and TX resulting, finally, in negative ΔA values. For PX, however, decrease in ΔA values at D/L of 0.05 is partially compensated at D/L of 0.1. We have tentatively explained these observations by invoking two competing forces in the overall drug–lipid interaction. One of these is an ‘in-plane’ force that tends to integrate the drug molecule to the plane formed by the lipid monolayer and the other is an ‘out-of-plane’ force that perturbs the drug and the lipid molecules such that the monolayer plane is no longer well defined.