Comparative In Vitro and In Vivo Evaluation of Fenofibric Acid as an Antihyperlipidemic Drug

Objectives:
Fenofibric acid (FA) is antihyperlipidemic agent and commercially available as a tablet formulation that weighs 840 mg for 105 mg of active substance. A new formulation with less inactive substance was developed as an alternative to the conventional formulation. The purpose of this study was to evaluate the dissolution and the relative bioavailability of the surface solid dispersion (SSD) and conventional formulations of FA by comparing them with the reference formulation in its commercial tablets. The in vitro-in vivo correlation among these tablet formulations was also evaluated.
Materials and Methods:
The dissolution study was performed in phosphate buffer pH 6.8 and biorelevant fasted state simulated intestinal fluid. Dissolution efficiency and mean dissolution time (MDT) were used to compare the dissolution profiles. The bioavailability study, using nine healthy volunteers, was conducted based on a single-dose, fasted, randomized, crossover design. The in vivo performance was compared using the pharmacokinetic parameters Cmax, Tmax, AUC0-72, and AUC0-∞. A linear correlation model was tested using MDT and mean residence time (MRT).
Results:
The results indicated that there were significant differences in the dissolution performances but no significant differences among the mean Cmax, Tmax, AUC0-72, or AUC0-∞ estimated from the SSD, conventional, and reference formulations. A poor correlation was found between MRT and MDT of the three formulations.
Conclusion:
The SSD formulation led to an instantaneous dissolution of the drug due to the presence of the polymer and the physical structure of the SSD. The conventional formulation could not achieve rapid dissolution despite its satisfying the requirement for immediate drug release dosage form. Both formulations could be considered bioequivalent with the reference. The in vitro dissolution behavior of FA using a single medium did not reflect their in vivo properties in the fasted condition. There was no correlation between the in vitro dissolution and the in vivo bioavailability of FA in this condition.