title: Biodegradation behavior of gellan gum in simulated colonic media.
abstract: The objective of this investigation was to test the biodegradability of gellan gum in the presence of galactomannanase in order to explore its suitability for the development of colon-specific controlled delivery systems. Gellan beads containing azathioprine (AZA) were prepared by ionotropic gelation in the presence of Ca2+ ions and were coated with an enteric polymer, Eudragit S-100. The effects of the simulated colonic fluid (SCF, pH 7.4 phosphate buffer) containing 15 mg/mL of galactomannanase on the in vitro release profiles of uncoated and enteric-coated beads were investigated, and the morphological changes in the structure of uncoated beads were assessed by scanning electron microscopy (SEM). In addition, 1% solution of deacetylated gellan gum was prepared and several aliquots of the resulting solution were evaluated rheologically to determine the concentration- and time-dependent effects of galactomannanase. Based on the percent drug released at 2 h, approximately 10% greater amount of drug was released in the SCF containing galactomannanase when compared with the enzyme-free dissolution medium. Results of rheological studies demonstrated that effects of galactomannanase on the viscosity of gellan gum solution are concentration-dependent rather than time-dependent. A significant decrease in the viscosity was noted in the presence of galactomannanase at a concentration of 15 mg/ mL, indicating that the polysaccharide degraded in an enzymatic reaction. SEM micrographs showed a distinct disruption of the polymeric network in the SCF. Overall, the results suggest that gellan gum undergoes significant degradation in the presence of galactomannanase which in turn facilitates the drug release from beads in the SCF in a controlled manner, thus approving the suitability of gellan gum as a carrier for controlled colonic delivery.
authors.affiliation: Drug Delivery Systems Research Laboratory, College of Pharmacy and Allied Health Professions, St John's University, Jamaica, New York, USA. BSingh@Emisphere.com
authors.forename: Brahma N
authors.initials: BN
authors.lastname: Singh
authors.forename: Louis D
authors.initials: LD
authors.lastname: Trombetta
authors.forename: Kwon H
authors.initials: KH
authors.lastname: Kim
mesh_terms: D001379:Azathioprine / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005750:Gastric Juice; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000201:enzymology; D008361:Mannosidases / Q000737:chemistry / Q000493:pharmacokinetics / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000145:classification / Q000493:pharmacokinetics; D011134:Polysaccharides / Q000737:chemistry / Q000493:pharmacokinetics / Q000648:ultrastructure; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D013678:Technology, Pharmaceutical; D013997:Time Factors; D014783:Viscosity / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; C038300:methylmethacrylate-methacrylic acid copolymer; C048288:gellan gum; D008361:Mannosidases; C109435:galactomannanase; D001379:Azathioprine