Acta Pharm. 56 (2006) 299-310[ Full paper in PDF ]
Pellets containing theophylline as a model drug and microcrystalline cellulose, in a ratio of 6:4, were prepared by the extrusion-spheronization method. The pellets were coated with Eudragit® RS aqueous dispersions, containing various amounts of pectin-chitosan complex and different coating mass gains, using a fluidized-bed apparatus. Twelve formulations were developed, which differed in two factors: coating mass gain (10, 15 and 20%, m/m) and the amount of pectin-chitosan complex (5, 10, 15 and 20%, m/m). Drug release studies were conducted using the USP apparatus I (basket) in dissolution media, mimicking the conditions prevailing in the stomach, small intestine or colon. Studies have shown that the drug release rate and pattern were dependent on both of the two mentioned factors. Some formulations showed bimodal and burst drug release, being triggered in the colonic medium by the action of pectinolytic enzymes. In formulations with 15 or 20% (m/m) of coating mass gain and 5 or 10% (m/m) of pectin-chitosan, the burst drug release was eliminated and replaced by the lag phase of drug release. In the case of burst drug release in the colonic medium, formulations with 20% (m/m) of coating mass gain and 15 or 20% (m/m) of pectin-chitosan were found to be better than the other formulations. Studies on the surface SEMs of uncoated and coated pellets show that after coating, coated pellets become smoother and exposure to pectinolytic enzymes in the colonic medium may result in surface erosion.
Keywords: bimodal drug delivery, burst release, chitosan, Eudragit® RS, mixed-film coating, pectin, pellet