In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of ibuprofen

The major aims of the present study were (1) to select a multiple-unit formulation that matched the in vitro dissolution profile of single-unit sustained-release commercial capsules, (2) to compare the sustaining/controlling efficacy of the selected multiple-unit formulation with that of the single-unit commercial conventional tablet and sustained-release capsules, and (3) to determine whether an in vitro-in vivo correlation exists for single- and multiple-unit formulations. Ibuprofen (20%–60% wt/wt)-loaded multiple-unit polystyrene microparticles were prepared by an emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Fenlong-SR, 400 mg) were compared. Since the microparticles with 30% ibuprofen load showed a release profile comparable to that of the Fenlong-SR release profile, the microparticles with this drug load were considered to be the optimized/selected formulation and, therefore, were subjected to stability study and in vivo study in human volunteers. A single-dose oral bioavailability study revealed significant differences in C_max, T_max, t^1/2a, t^1/2e, K_a, K_e, and AUC between the conventional tablet and optimized or Fenlong-SR capsule dosage forms. However, all the parameters, with the exception of K_a along with relative bioavailability (F) and retard quotient (R_Δ), obtained from the optimized ibuprofenloaded microparticles were lower than that obtained from the commercial Fenlong-SR formulation. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution. Published: September 1, 2006