Enhanced percutaneous absoption of piroxicam via salt formation with ethanolamines

Purpose. The aim of this work was to prepare piroxicam-ethanolamine salts (PX-EAs) with improved physicochemical properties for transdermal application. Methods. The physicochemical properties of prepared salts were investigated by DSC and FT-IR. Their percutaneous absorption characteristics across hairless mouse skin and the effect of various enhancers were studied using a flow-through diffusion cell system. Results. Three piroxicam-ethanolamine salts were prepared. Piroxicam monoethanolamine salt (PX-MEA) and piroxicam diethanolamine salt (PX-DEA) had higher solubility than piroxicam in most of vehicles tested and a higher permeation rate across the skin. The solubility and permeation rate of piroxicam triethanolamine salt (PX-TEA) was lower than those of piroxicam in most of vehicles tested. However, there was no significant change in octanol/water partition coefficient by salt formation. Salt formation lowered the melting point of piroxicam and, of the systems examined, PX-DEA showed the lowest melting point. When the effect of various enhancers were evaluated, nonionic surfactants having medium HLB, an alkyl chain length of C18 and an ethylene oxide chain were better able to modify the permeability of the stratum corneum and to promote the effective penetration of piroxicam and PX-EAs. Conclusions. Piroxicam salt formation with MEA and DEA improved the physicochemical properties and enhanced the skin permeability of piroxicam.