OPTIMIZATION OF METHODS FOR SYNTHESIS OF FENOFIBRIC ACID AND ITS DERIVATIVES AS ANTI-HYPERLIPIDEMIC DRUGS AND REFERENCE STANDARD FOR FENOFIBRATE DRUG SAFETY

• Main Author: Dinny
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/64664
• Institution: Institut Teknologi Bandung

Fenofibric acid belongs to the group of fibrates under the trade names Trilipix or Fibricor. Fenofibric acid is an activator of PPAR-? (peroxisome proliferator-activated receptors) which has antihyperlipidemic activity so that it reduces the increase in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, apolipoprotein B, and increases high-density lipoprotein cholesterol (HDL-C). Fenofibric acid in combination with statins has better activity than other fibrates. Fenofibric acid is also known as impurity B in the synthesis of fenofibrate so that it serves as a standard reference in the synthesis of the active raw material for the drug fenofibrate. The fenofibric acid synthesis method in previous studies had several drawbacks such as solvents with high toxicity, complicated and expensive separation processes and long synthesis times. Therefore, optimization of the phenofibric acid synthesis method was carried out in the aqueous phase and the liquid phase mediated DMImBr ion solution to support the concept of green chemistry. The results showed that the use of solvents (methanol/ethanol/2-propanol) and liquid DMImBr ion could be used in the synthesis of phenofibric acid. The highest % yield was obtained using DMImBr+ethanol ionic liquid through reflux heating, which was 97.2% for 5 hours at 74-75oC. The Rf value of the product was 0.6 with n-hexane:ethyl acetate:diethyl ether:glacial acetic acid as eluent = 5:10:2:1 (v/v). The melting point of the fenofibric acid product is 176.1-179.3oC with a percent error of 0.16%. The product is white in color and has been characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Fenofibric acid is then synthesized to form phenofibric acid methyl ester known as impurity D through an esterification reaction using concentrated sulfuric acid as a catalyst. The results showed that the yield of fenofibric acid methyl ester was 61.4% for 10 hours at 64-65oC. The Rf value of the product was 0.98 with n-hexane as eluent: ethyl acetate:glacial acetic acid=3:7:1 (v/v). The product obtained is white in color with a melting point of 68.4oC. Confirmation of product compound structure using FTIR, 1H-NMR, and 13C-NMR spectroscopy.