Preparation and Characterization of a Eutectic Mixture of Fenofibric Acid and Nicotinic Acid and Evaluatuion of In Vivo Antihyperlipidemic Activity

Abstract

Fenofibric Acid (FA) is classified under Biopharmaceutical Classification System (BCS) class II due to its poorly soluble in water and high permeability. The present study aimed to prepare the eutectic mixture of FA with nicotinic acid (NA) and characterize its solid state properties and in vitro dissolution rate, along with its in vivo antihyperlipidemic activity. Solvent drop grinding was the method chosen to prepare the eutectic mixture of FA and NA. Solid-state properties were evaluated using thermal analysis Differential Scanning Calorimetry (DSC), crystallographic analysis Powder X-Ray Diffraction (PXRD), FT-IR spectroscopic analysis, and Scanning Electron Microscopy (SEM). To examine in vivo antihyperlipidemic activity, 16 male Swiss Webster rats were injected with 1% hyperlipidemia-inducing solution, followed by the oral administration of 9.45 mg/kg FA and NA (equivalent to 9.45 mg/kg FA), after which the decrease in cholesterol levels was measured. Two-way ANOVA was used to evaluate the data, followed by Duncan’s multiple range test (95% confidence interval). The results proved that FA formed the eutectic mixture with NA at a molar ratio of 6:4. The eutectic mixture of FA-NA had a better solubility and in vitro dissolution rate compared to intact FA, which also led to notably improved antihyperlipidemic activity.

Eutectic Mixture of Fenofibric Acid and Syringic Acid: Improvement of Dissolution Rate and Its Antihyperlipidemic Activity

“…The PXRD patterns of fenofibric acid and syringic acid are similar to those reported in a recent study by Anggraini et. al [19] . and Haneef & Chadha [20] .…”

“…al. [19] and Haneef & Chadha. [20] The diffractogram of fenofibric acid shows intense and characteristic peaks at 2 theta = 15.8707, 18.4275, and 23.0899, while syringic acid demonstrates specific peaks at 2 theta = 13.4971 and 22.4931, indicating a highly crystalline nature.…”

Improving the Solubility of Fenofibric Acid via Multicomponent Crystal Formation with Theobromine Coformer

“…3 So, it is necessary to increase the solubility of poorly soluble APIs. Various efforts have been made to increase the solubility of FA, such as the addition of MgCO3 and carrageenan catalysts, 4 formations of ternary solid dispersions with hyaluronic acid and polyethyleneglycol, 5 salt formation with choline bases, diethanolamine, tromethamine, calcium, ethanolamine, and piperazine, 6 formations of surface solid dispersions using sodium croscarmellose, 7 formations of self nanoemulsions, 8 multicomponent crystals of eutectic mixtures with nicotinamide and nicotinic acid coformers, 9,10 and formation of multicomponent crystals with saccharin coformers. Increasing the solubility of active pharmaceutical ingredients by forming multicomponent crystals is a popular method nowadays because the APIs are produced in the form of crystalline phases.…”

Increasing the Solubility and Anti-Inflammatory Activity of Curcumin by Cocrystallization

“…A multicomponent solid is formed from an API and a coformer, resulting in a new solid phase (Haneef and Chadha, 2017;Palanisamy et al, 2019). The API can be prepared into a multicomponent solid with certain coformer so the solubility can increase (Haneef and Chadha, 2017;Chavan and Shastri, 2018;Wicaksono et al, 2021;Anggraini et al, 2022).…”