Partially quarternized amino functional poly(methacrylate) terpolymers: versatile drug permeability modifiers.

Area of Science:

• Polymer Chemistry
• Biopharmaceutics
• Materials Science

Background:

• Basic butylated methacrylate copolymer (BBMC/EUDRAGIT E) is an FDA-approved excipient.
• BBMC is primarily used for tablet coatings.
• Polymer modification offers a route to novel functional materials.

Purpose of the Study:

• To synthesize and characterize partially quarternized poly(methacrylate) terpolymers (Q-BBMCs).
• To evaluate the efficacy of Q-BBMCs as permeation enhancers.
• To investigate the pH-dependent activity and recovery of Q-BBMCs.

Main Methods:

• Synthesis of Q-BBMCs with varying degrees of quarternization (22%, 42%, 65%).
• Assessment of apical to basolateral transport across Caco-2 cell monolayers using trospium and mannitol.
• Measurement of transepithelial electrical resistance (TEER) to evaluate barrier integrity.

Main Results:

• Q-BBMCs significantly increased the permeation of trospium and mannitol at pH 6.5 (up to 7.3-fold enhancement).
• Q-BBMCs demonstrated sustained activity as permeation enhancers over a broader pH range (up to pH 7.4) compared to BBMC.
• TEER measurements showed rapid recovery of cell monolayer integrity after Q-BBMC exposure.

Conclusions:

• Partially quarternized poly(methacrylate) terpolymers are effective permeation enhancers.
• Q-BBMCs offer an extended effective pH range for drug delivery applications.
• The developed Q-BBMCs show potential for improving oral drug absorption.