Inclusion complexation of weakly acidic NSAID with β-cyclodextrin: selection of arginine, an amino acid, as a novel ternary component

Abstract

The purpose of the present study was to investigate the influence of an amino acid, arginine, as a ternary component on the complexation of Lornoxicam, a poorly water-soluble and weakly acidic anti-inflammatory agent, with β-cyclodextrin (β-CD). The molecular inclusion of Lornoxicam with βCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate limited oral absorption. The solid complexes of Lornoxicam and β-CD with or without arginine (binary and ternary systems, respectively) were prepared as Freeze dried product in different stoichiometric ratios. The formation of inclusion complexes in solid state was confirmed by using classical instrumental techniques like IR, DSC, XRD, and in liquid state by phase solubility analysis, UV spectroscopy, HPLC and 1H NMR. The in vitro dissolution and the saturation solubility of complex are determined analyzing by UV spectrophotometer. Assay and level of related substance was monitored by developed RP-HPLC method. Inclusion ternary complex of Lornoxicam with β-CD and arginine showed significant improvement in dissolution compared with uncomplexed drug and binary system. This improved physicochemical behavior of ternary complex with the novel inclusion of an arginine translated into enhanced in vitro dissolution of Lornoxicam compared with standard rapid marketed formulation.