Controlled release of substituted benzoic and naphthoic acids using Carbopol gels: measurement of drug concentration profiles and correlation to release rate kinetics.

PURPOSE

The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol matrices containing mesalamine or benzoic acid.

METHODS

Release rate experiments with Carbopol matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration.

RESULTS

The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93-95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices.

CONCLUSIONS

The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol gel layer and drug diffusivity.