Comparative in vitro and in vivo evaluation of fenofibric acid as anti-hyperlipidemic drug

INTRODUCTION: Fenofibric acid (FA) is antihyperlipidemic agent and commercially available as a tablet formulation weighs 840 mg for 105 mg active substance. A new formulation with less inactive substance was developed as an alternative to conventional formulation. The purpose of this study was to evaluate the dissolution study and the relative bioavailability of the surface solid dispersion (SSD) and conventional formulations of FA by comparing them to the reference formulation in its commercial tablets. The in vitro-in vivo correlation (IVIVC) among these tablet formulations was also evaluated.
METHODS: The dissolution study was performed in phosphate buffer pH 6.8 and biorelevant Fasted State Simulated Intestinal Fluid (FaSSIF). Dissolution efficiency (DE) and mean dissolution time (MDT) was 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 pharmacokinetic parameters Cmax, Tmax, AUC0-72, and AUC0-∞. Linear correlation model was tested using MDT and mean residence time (MRT).
RESULTS: The results indicated that there were significant differences found in the dissolution performances and no significant differences observed among the mean Cmax, Tmax, AUC0-72, and AUC0-∞, estimated from the SSD, conventional, and reference formulations.Poor correlation was found between MRT and MDT of three formulations.
DISCUSSION AND CONCLUSION: The SSD formulation led to an instantaneous dissolution due to the presence of the polymer and physical structure of the SSD. The conventional formulation could not achieve rapid dissolution despite it satisfied the requirement for immediate drug release dosage form. The both formulations could be considered bioequivalent with reference.The in vitro dissolution behavior of fenofibric acid using single medium did not reflect their in vivo properties at the fasted condition. There was no correlation between the in vitro dissolution and the in vivo bioavailability of fenofibric acid at this condition.