title: Mechanistic analysis of drug release from theophylline pellets coated by films containing pectin, chitosan and Eudragit RS.
abstract: The objective of this study was to obtain detailed information on the mechanism of drug release from mixed-film of pectin-chitosan/Eudragit RS. Pellets (710-840 microm in diameter) containing 60% theophylline and 40% microcrystalline cellulose were prepared by extrusion-spheronization method. Eudragit L100-55 enteric coating capsules included film-coated pellets of theophylline in theoretical coating weight gains of 10, 15, and 20%, with pectin-chitosan complex contents of 5, 10, 15, and 20% for each level of weight gain were prepared and subjected to in vitro drug release. Drug release from this system showed a bimodal release profile characteristic with the drug release enhancement, being triggered (burst release) in the colonic medium. The reason for burst drug release may be due to the enzymatic degradation of pectin via pectinolytic enzymes in the simulated colonic medium. The mechanism of drug release from each formulation was evaluated in the terms of zero-order, first-order, Higuchi and Korsmeyer-Peppas models. It was observed that none of the enteric coating capsules showed any drug release in the simulated gastric medium (phase I). The analysis of release profiles showed that zero-order kinetics was found as the better fitting model for all formulations in the simulated small intestine (phase II) and it could be due to the pectin-chitosan swelling and subsequent formation of aqueous channels. In the colonic medium (phase III), due to degradation of pectin and its leaching from the mixed-film, there was a modification in drug release kinetics from swelling-controlled at phase II to anomalous at phase III. It also was found that both zero-order and Higuchi models contributed in colonic drug release from most of the formulations.
authors.affiliation: Rouz Darou Pharmaceutical Company, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ghaffari
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Avadi
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Moghimi
authors.forename: Mahvash
authors.initials: M
authors.lastname: Oskoui
authors.forename: Khosrow
authors.initials: K
authors.lastname: Bayati
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002214:Capsules; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008954:Models, Biological; D010368:Pectins / Q000737:chemistry; D013678:Technology, Pharmaceutical; D013806:Theophylline / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D002214:Capsules; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; D005079:Excipients; C050528:Eudragit RS; D010368:Pectins; D002482:Cellulose; D048271:Chitosan; D013806:Theophylline; C109691:microcrystalline cellulose