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

Abstract

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 (Δ A) of DMPC monolayer due to the presence of drugs. All three drugs could be integrated in the monolayer resulting in a positive value of Δ A for D/L ratio of 0.026. Above this D/L value, there is an anomalous, monotonic decrease in Δ A for MX and TX resulting, finally, in negative Δ A values. For PX, however, decrease in Δ A 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.