Developing Quantitative In Vitro-In Vivo Correlation for Fenofibrate Immediate-Release Formulations With the Biphasic...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery and Formulation

Background:

• Fenofibrate (FEN) is a widely used lipid-lowering agent.
• Evaluating the in vitro-in vivo correlation (IVIVC) of different FEN formulations is crucial for predicting in vivo performance.
• Biorelevant media and hydrodynamic conditions significantly influence drug dissolution and absorption.

Purpose of the Study:

• To evaluate three fenofibrate formulations (Fournier®, Lipidil®, HME tablet) using an in vitro biphasic dissolution method.
• To establish a quantitative in vitro-in vivo correlation (IVIVC) for fenofibrate absorption.
• To assess the impact of biorelevant media and hydrodynamic conditions on fenofibrate release.

Main Methods:

• Utilized an in vitro biphasic dissolution method with biorelevant media (Simulated Intestinal Fluid v2).
• Investigated United States Pharmacopeia (USP) IV flow rate and paddle speed effects on FEN release.
• Obtained in vivo pharmacokinetic profiles under fasting and fed states, deconvoluted using the Wagner-Nelson method.

Main Results:

• The biphasic method accurately predicted in vivo absorbed fenofibrate amounts under fed conditions with appropriate hydrodynamic settings.
• Under fasted conditions, the in vitro octanol partitioning significantly underestimated in vivo absorption.
• The biphasic test overestimated the positive food effect for Fournier® capsules, while no food effect was observed for HME and Lipidil® tablets in vivo.

Conclusions:

• The in vitro biphasic method can achieve quantitative IVIVC for fenofibrate under fed conditions.
• Careful selection of biorelevant media and hydrodynamic parameters is essential for accurate IVIVC.
• The method requires further refinement to accurately predict fenofibrate absorption under fasted conditions and food effects for all formulations.