Adsorption of an ionizable drug onto microspheres: experimental and modeling studies

The purpose of this work was to study the in vitro equilibria and the adsorption kinetics of an ionizable drug, indomethacin, onto commercially available cationic polymeric microspheres: DEAE Trisacryl LS and QA Trisacryl LS. Isotherms were fitted to theoretical equations allowing accurate predictions of drug loading at different salt concentrations. Isotherm measurements were quickly obtained by simple column breakthrough experiments. The nature of the ion exchange group of the microspheres was observed to be preponderant for adsorption, as the tertiary amine derivative exhibited 53% more capacity than its quaternary amine counterpart. The maximum equilibrium uptake capacity in a 5 mM Tris-HCl buffer at pH 7.4 is 303 mmol/ml of particle volume, for DEAE microspheres. Transport properties of indomethacin into the tertiary amine microspheres were obtained in agitated contactor. Microbeads loading was completed in a 1-6 min range and was found to be controlled by pore diffusion mechanism. Equilibrium uptake data was fitted to the Langmuir and the mass action law models. Adsorption kinetics were fitted to a pore diffusion model. Good correlation was obtained between the theoretical models and the experimental data. The methodology outlined in this work provided a simple approach of estimating adsorption behavior of drugs onto ion-exchange macroporous microspheres. Although significant indomethacin loading was obtained onto the DEAE microspheres, the rapid rate of diffusion is not compatible with sustained release properties sought for this type of microspheres.