Abstract

Purpose: The purpose of this study was to develop roxithromycin (ROX) sustained-release pellets by coating matrix beads containing Carbopol^® 974P and octadecanol. Method: The sustained release pellets were prepared by the extrusion-spheronization technique and subsequently coated with aqueous dispersion mixtures of Eudragit^® NE30D and Eudragit^® L30D-55. In vivo, the relative bioavailability of the sustained release pellets were studied using 36 healthy volunteers who took single doses and multiple doses of 300 mg ROX sustained-release pellets and commercially available sustained-release tablets, used as a reference, in a randomized self-crossover design. Results: The optimal formulation of the pellets involved ROX (76%), Carbopol^® 974P (2%), microcrystalline cellulose (MCC) (18%), octadecanol (2%) and Na₂CO₃ (2%). The dissolution results showed that when the concentration was 3%, the coating mixture which contained Eudragit^® NE30D and L30D-55 (the ratio was 8:2) gave comparatively better release profiles and the expected release rates during testing. In vivo, the C_max value of ROX sustained-release pellets was 7.08±1.53 μg/ml and that of commercial sustained-release tablets was 7.01±0.94 μg/ml while the corresponding values t_max values were 3.83±0.79 h and 4.17±0.51 h for a single dose. Following multidoses, the values were 7.17±0.94 μg/ml and 6.96±0.45 μg/ml, and 3.67±0.69 h and 4.06±0.73 h, respectively. The relative bioavailability of ROX sustained pellets as a single dose and multidoses was 101.1%±8.3% and 100.39%±6.4%, respectively. Conclusion: ROX sustained-release pellets and the reference commercial tablets are bioequivalent.

Keywords:  Roxithromycin   Extrusion-spheronization   Sustained-release pellets   Bioequivalence