Mechanistic studies on effervescent-induced permeability enhancement

Area of Science:

• Pharmacology
• Gastroenterology
• Biophysics

Background:

• Intestinal drug absorption is limited by epithelial barriers.
• Effervescent formulations are explored for enhanced drug delivery.

Purpose of the Study:

• To elucidate the mechanisms of effervescence-induced penetration enhancement across the intestinal epithelium.
• To investigate the impact of carbon dioxide (CO2) bubbling on drug permeability for various compounds.

Main Methods:

• In vitro studies using a modified Ussing chamber.
• In vivo investigations employing single-pass intestinal perfusion.
• Measurement of transepithelial electrical resistance (TEER) and paracellular marker flux.

Main Results:

• CO2 bubbling increased drug permeability without causing significant cell membrane damage.
• TEER reduction indicated structural changes in the paracellular pathway, not cellular damage.
• Flux of paracellular markers showed a molecular weight dependence, confirming pathway alteration.
• Tissue recovery was observed within approximately 20 minutes.

Conclusions:

• CO2 bubbling enhances intestinal drug permeability primarily through paracellular pathway alteration.
• The observed effects are attributed to structural changes in the paracellular pathway, fluid flow, and membrane hydrophobicity.
• Effervescent-induced penetration enhancement offers a promising strategy for improving oral drug bioavailability.