IVIVR in oral absorption for fenofibrate immediate release tablets using dissolution and dissolution permeation...

Area of Science:

• Pharmaceutical Sciences
• Pharmacokinetics
• Drug Delivery Systems

Background:

• Previous studies showed a dissolution/permeation (D/P) system could differentiate fenofibrate formulations and correlate with rat in vivo exposure.
• Immediate-release fenofibrate formulations require careful assessment for consistent in vivo performance.

Purpose of the Study:

• To investigate human pharmacokinetic data for six fenofibrate tablet formulations.
• To evaluate the role of dissolution and permeation in predicting in vivo fenofibrate performance, specifically Cmax.
• To understand how formulation excipients, like surfactants, influence fenofibrate's bioavailability.

Main Methods:

• Analysis of pharmacokinetic data (AUC, Cmax) from human in vivo studies of six fenofibrate tablet formulations.
• Utilized a permeation system with dialysis membranes to assess the impact of micellar entrapment by surfactants.
• Correlated in vitro dissolution profiles with in vivo pharmacokinetic parameters.

Main Results:

• No significant differences in Area Under the Curve (AUC) were observed between fenofibrate formulations in humans.
• Significant differences in Maximum Concentration (Cmax) were found but were not explained by dissolution alone.
• Permeation studies demonstrated that surfactants caused micellar entrapment and reduced fenofibrate mobility, explaining Cmax variations.

Conclusions:

• Permeation, in addition to dissolution, is crucial for establishing accurate in vitro-in vivo correlations (IVIVC) for fenofibrate.
• Surfactant-mediated micellar entrapment significantly impacts the Cmax of fenofibrate, a factor not captured by dissolution testing alone.
• The D/P system, incorporating a permeation step, offers a more robust prediction of in vivo drug performance compared to dissolution alone.