Biorelevant media simulating fed state intestinal fluids: colloid phase characterization and impact on solubilization...

Area of Science:

• Pharmacokinetics and Drug Delivery
• Colloid and Interface Science
• Gastrointestinal Physiology

Background:

• Fed state intestinal fluids (SIFs) are complex colloidal systems crucial for drug absorption.
• Understanding the nanostructural composition of SIFs is vital for predicting drug solubilization.
• Lipolysis products significantly alter the structure and properties of intestinal fluids.

Purpose of the Study:

• To investigate how free fatty acid and monoglyceride levels and ratios impact SIF nanostructure.
• To determine the effect of these compositions on the solubilizing capacity of SIFs for poorly water-soluble drugs.
• To correlate SIF nanostructure with drug solubility and identify key influencing factors.

Main Methods:

• Preparation and characterization of simulated intestinal fluids (SIFs) with varying oleic acid/monoolein ratios.
• Utilized surface tension, dynamic light scattering, and cryogenic transmission electron microscopy for nanostructural analysis.
• Assessed solubilizing capacities for danazol, fenofibrate, and cinnarizine.

Main Results:

• SIF nanostructure varied with lipolysis product content, forming micelles, vesicles, and other colloidal structures.
• Higher oleic acid/monoolein ratios (6:1) resulted in more numerous and well-defined colloidal structures.
• Nanostructural composition influenced the solubilizing capacity for fenofibrate and cinnarizine, but not danazol.

Conclusions:

• The relative composition of simulated intestinal fluids is critical for the solubilizing capacity of certain drug compounds.
• Drug affinity for specific colloidal structures within SIFs dictates its solubility.
• These findings highlight the importance of SIF nanostructure in oral drug bioavailability.