Mechanistic analysis and experimental verification of bicarbonate-controlled enteric coat dissolution: Potential in...

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Drug Delivery

Background:

• Enteric coatings (EC) are designed for targeted drug release in the intestine.
• Traditional in vitro dissolution tests often fail to accurately predict in vivo performance of EC products.
• In vivo dissolution of EC products is frequently slower than anticipated, necessitating a deeper mechanistic understanding.

Purpose of the Study:

• To investigate the influence of bulk pH and bicarbonate molarity on the dissolution profiles of enteric-coated products.
• To elucidate the mechanistic reasons behind the discrepancies between in vitro and in vivo dissolution rates of enteric coatings.
• To identify key factors governing enteric coating performance in the intestinal environment.

Main Methods:

• Evaluation of enteric-coated (EC) product release properties under varying bulk pH and bicarbonate molarity conditions.
• Comparative analysis of dissolution rates at physiologically relevant in vivo conditions.
• Investigation of carbonic acid and carbon dioxide hydration/dehydration kinetics within the diffusion layer.

Main Results:

• Bicarbonate molarity was found to be a more critical determinant of enteric coating dissolution than bulk pH at in vivo-relevant conditions.
• The dissolution of enteric coatings exhibits a steep dependence on bicarbonate molarity, impacting in vivo performance.
• Sub-equilibrium kinetics of carbonic acid/carbon dioxide in the diffusion layer lead to a lower effective pKa of bicarbonate.

Conclusions:

• The limited performance of enteric coatings in vivo is attributed to low intestinal bicarbonate concentrations.
• Accurate assessment of enteric drug products requires thorough investigation of intestinal bicarbonate levels.
• Utilizing bicarbonate buffers or appropriate surrogates in development and quality control is crucial for reliable enteric coating evaluation.