Dissolution Rate Enhancement and Physicochemical Characterization of a Fenofibric Acid–Nicotinamide Eutectic Mixture doi.org/10.26538/tjnpr/v5i9.14

Abstract

Fenofibric acid is a potent lipid-lowering agent that is used clinically in severe hypertriglyceridemia, primary hyperlipidemia, and mixed dyslipidemia. Fenofibric acid is a poorly soluble drug which is classified as a Biopharmaceutical Classification System (BCS) class II. The purpose of the present study was to improve the solubility and dissolution rate of the poorly soluble drug fenofibric acid (FA) by the formation of a simple eutectic mixture with nicotinamide (NIC). A simple eutectic mixture of FA and NIC was prepared using the solvent-drop grinding method. A binary phase diagram of FA and NIC in various molar ratios was constructed by thermal analysis differential scanning calorimetry (DSC). Solid-state characterization was carried out using powder X-ray diffraction (PXRD) analysis, differential scanning calorimetry, Fourier transform-infrared spectroscopy analysis, scanning electron microscopy analysis, and apparent solubility test. The in vitro dissolution rate of the simple eutectic mixture in an aqueous medium was determined using a type I USP apparatus. The binary phase diagram demonstrated that FA and NIC form a simple eutectic mixture at a molar ratio of 0.3:0.7. The eutectic mixture melted at an endothermic peak of 112.9°C. The PXRD pattern of the eutectic mixture was representative of each intact component (FA and NIC). SEM microscopic analysis showed that new crystal habits were formed. The solubility and dissolution rate of FA from the eutectic mixture were improved significantly compared to intact FA.