title: Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.
abstract: Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.
authors.affiliation: a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Rai
authors.affiliation: a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , India.
authors.forename: Awesh K
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , India.
authors.forename: Narendra K
authors.initials: NK
authors.lastname: Jain
authors.affiliation: a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , India.
authors.forename: Govind P
authors.initials: GP
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004811:Epichlorohydrin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D008863:Microspheres; D051381:Rats; D013608:Tablets, Enteric-Coated; D014961:X-Ray Diffraction
chemical_list: D003432:Cross-Linking Reagents; D003911:Dextrans; D004337:Drug Carriers; D013608:Tablets, Enteric-Coated; D004811:Epichlorohydrin
keywords: 5-FU; Colon cancer; enzymatic degradation; organ distribution; pharmacokinetic