Advanced Optimization of Variations in Synthesis Method and Effects of Ionic Liquid Medium in the Synthesis of Meloxicam as non-Steroidal anti-Inflammatory Drug Rozkananda Rohmah Agustin (a), Dr. Deana Wahyuningrum (a*), Aep Patah, Ph.D. (a)
a) Departement of Chemistry, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Ganesha Street 10, Bandung, 40132, Indonesia
*e-mail: deana[at]itb.ac.id
Abstract
Meloxicam is an oxicam derivative compound belonging to the NSAIDs (non-Steroidal anti-Inflammatory Drugs) group. Meloxicam has antiinflammation, analgesic, and antipyretic activity by inhibiting cyclooxygenase-2 to decrease the synthesis of prostaglandins in the body. Meloxicam can be used as osteoarthritis and rheumatoid arthritis drug medication orally. The meloxicam synthesis method published by previous researchers has several weaknesses, such as long reaction time, low %yield, and high production costs. Therefore, optimization to increase the %yield of the product while reducing production costs is required. Optimization in the solid phase includes irradiation time, preheating time, and total reaction time. At the same time, the solution phase includes optimization of temperature and total reaction time. Then for the solution phase ionic liquid mediated, there is an additional optimization in the form of the percentage of ionic liquid added. In this study, the optimization of the meloxicam synthesis method is performed by variations in solution phase, solid phase, and solution phase mediated ionic liquids, which are OMImBr (1-octyl-3-methylimidazolium bromide), DdMImBr (1-dodecyl-3-methylimidazolium bromide), BMImI (1-butyl-3-methylimidazolium iodide), DMImCl (1-decyl-3-methylimidazolium chloride), OMImBF4 (1-octyl-3-methylimidazolium tetrafluoroborate), OMImCl (1-octyl-3-methylimidazolium chloride), and OMImPF6 (1-octyl-3-methylimidazolium hexafluorophosphate). The ionic liquids can act as Lewis acids, so it is possible to catalyze the reaction synthesis of meloxicam. The meloxicam product has been successfully characterized using TLC, melting point, FTIR, 1H-NMR, and 13C-NMR spectroscopy. In the solution phase, the meloxicam compound has been successfully synthesized and characterized with the highest yields of 92%, with o-xylene solvent for 24 hours at 144oC with reflux heating. In the solid phase, the meloxicam compound has been successfully synthesized and characterized with the highest yields of 78% with preheating for 3 minutes, irradiation time for 10 seconds, pausing for 10 seconds, and 2 minutes total reaction time using a domestic microwave. The Rf value of product is 0.39 with mobile phases ethyl acetate: n-hexane = 1:1 (v/v) and stationary phase silica. The addition of ionic liquid in the meloxicam synthesis reaction can reduce the yields of the resulting product. The variations of cations that produce greater yields successively started from BMImI<OMImBr<DMImBr<DdMImBr. Variations of anions that produced greater yields successively started from OMImCl<OMImBr<OMImBF4<OMImPF6.
