Buccal drug absorption. II: In vitro diffusion across the hamster cheek pouch.

Area of Science:

• Pharmacokinetics
• Drug Delivery
• Biomaterials Science

Background:

• Understanding drug diffusion across biological barriers is crucial for predicting in vivo absorption.
• The hamster cheek pouch is a potential in vitro model for studying drug permeation.
• Substituted acetanilides serve as model compounds for diffusion studies.

Purpose of the Study:

• To investigate the in vitro diffusion of substituted acetanilides across the hamster cheek pouch.
• To determine the correlation between in vitro permeability and physicochemical properties.
• To evaluate the utility of the hamster cheek pouch model for predicting human buccal absorption.

Main Methods:

• In vitro diffusion studies using excised hamster cheek pouch.
• Measurement of epithelial permeability (Pe) for a series of substituted acetanilides.
• Correlation analysis with physicochemical parameters like octanol-buffer (PCoct) and isooctane-buffer (PCiso) partition coefficients.
• Comparison of in vitro data with in vivo human buccal absorption data.

Main Results:

• The keratinized epithelial layer of the hamster cheek pouch significantly hindered compound diffusion.
• Linear relationships were observed between log epithelial permeability (Pe) and partition coefficients (log PCoct, r=0.712; log PCiso, r=0.869).
• A strong correlation (r=0.878) was found between in vitro Pe and in vivo human buccal absorption percentages within 5 minutes.

Conclusions:

• The hamster cheek pouch epithelium presents a major barrier to acetanilide diffusion.
• Physicochemical properties, particularly lipophilicity, influence drug permeability across this model.
• The hamster cheek pouch in vitro model demonstrates potential for predicting human buccal drug absorption.