Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability

Area of Science:

• Pharmacology
• Physical Chemistry
• Drug Development

Background:

• Assessing intestinal permeability is crucial for drug classification.
• The biopharmaceutical classification (BCS) system categorizes drugs based on absorption characteristics.
• Existing methods for permeability assessment can be complex.

Purpose of the Study:

• To evaluate the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability.
• To determine if CLFR can be effectively used in the biopharmaceutical classification (BCS) of passively absorbed drugs.

Main Methods:

• CLFR was determined using thermodynamic parameters (melting point, molar fusion enthalpy, entropy) obtained via differential scanning calorimetry.
• Input parameters included dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate.
• Thermodynamic parameters were derived from differential scanning calorimetry measurements.

Main Results:

• CLFR values ranged from 0.06-41.76 mole percent.
• A strong correlation (r > 0.8) was observed between CLFR and in vivo intestinal permeability.
• CLFR values above 2 mole percent indicated complete intestinal absorption.
• Over 92% of tested drugs were correctly classified using CLFR in relation to dose number or dissolution rate, aligning with the BCS system.

Conclusions:

• CLFR is a potential parameter for quantitative biopharmaceutical classification.
• CLFR may serve as a surrogate for permeability studies, reflecting solubility in lipid bilayers.
• This approach facilitates the characterization of all four BCS drug classes based on absorption properties.