Complex Formation of Etodolac with Hydrotalcite in Methanol

Abstract

Abstract Etodolac (2-[(1RS)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl]acetic acid) is a nonsteroidal anti-inflammatory drug (NSAID) with a bitter taste. It is slightly soluble in water. Hydrotalcite is a carbonate-type MgAl-layered double hydroxide (CO3-LDH) that is used as an antacid. A complex of etodolac with hydrotalcite was synthesized in methanol via an ion-exchange reaction. The carboxy groups of etodolac were exchanged with carbonate ions in the interlayer region of CO3-LDH. Ion exchange was confirmed by IR and 13C CP/MAS NMR spectra. The complex of nitrate-type LDH (NO3-LDH) was obtained in a mixed solvent composed of equal volumes of methanol or ethanol, and water. The complex had an interlayer distance of 2.20 nm, and a bilayer structure of etodolac in the interlayer region of the complex was observed. The uptake amount increased to 3.0 mmol per gram of CO3-LDH depending on the concentration of etodolac, reaction temperature, and reaction time. The etodolac in the interlayer region of the complex was completely released after 120 min in phosphate buffer. The release of etodolac occurred through exchange with phosphate ions. Thus, the bitterness of etodolac can be suppressed by coating it with LDH.