ADVANCED OPTIMIZATION OF VARIATIONS IN SYNTHESIS METHOD AND EFFECTS OF IONIC LIQUID STRUCTURE IN SYNTHESIS OF MELOXICAM AS NONSTEROIDAL ANTIINFLAMMATORY DRUG

• Main Author: Rohmah Agustin, Rozkananda
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/71625
• Institution: Institut Teknologi Bandung

Meloxicam is an oxicam derivative compound belonging to 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 acts as a noncompetitive inhibitor by changing the shape of cyclooxygenase-2 active site. Meloxicam can be used as osteoarthritis and rheumatoid arthritis drug medication orally. The meloxicam synthesis method published by previous researchers has several weakness, such as long reaction time, the low %yield, and the high of 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. Whereas for 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 meloxicam synthesis method are performed by variations in solution phase, solid phase, and solution phase mediated ionic liquids 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). Ionic liquid can act as Lewis acid so that it is possible to catalyze the reaction synthesis of meloxicam. The obtained meloxicam product has been successfully characterized using TLC (Thin Layer Chromatography), melting point, FTIR (Fourier Transform Infra Red), 1H-NMR (Nuclear Magnetic Resonance), and 13C-NMR spectroscopy. In the solution phase, meloxicam compound has been successfully synthesized and characterized with the highest %yield of 92% using o-xylene solvent during 24 hours at 144 oC reaction temperature with reflux heating. In the solid phase, meloxicam compound has been successfully synthesized and characterized with the highest %yield of 78% with preheating for 3 minutes, irradiation time for 10 seconds, pausing for 10 seconds, and 2 minutes total reaction time by using a domestic microwave. A greater %yield successively start from BMImI<OMImBr<DMImBr<DdMImBr. This is due to the carbon atoms chain addition of the alkyl group which causes polarity decrease. By using 2,5% (v/v) DdMImBr ionic liquid, meloxicam compound has been successfully synthesized and characterized with %yield of 29,78% using o-xylene solvent during 24 hours at 144 oC reaction temperature with reflux heating. A greater %yield successively start from OMImCl<OMImBr< OMImBF4<OMImPF6. This is due to the polarity decrease and bulkier anion structure. By using 2,5% (v/v) OMImPF6 ionic liquid, meloxicam compound has been successfully synthesized and characterized with %yield of 25,02% using o-xylene solvent during 24 hours at 144 oC reaction temperature with reflux heating. Rf value is 0.39 with mobile phases ethyl acetate:n-hexane = 1:1 (v/v) and stationary phase silica