Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.
Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.
a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , Madhya Pradesh , India.
Gopal
G
Rai
a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , Madhya Pradesh , India.
Awesh K
AK
Yadav
a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , Madhya Pradesh , India.
Narendra K
NK
Jain
a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences , Dr. Hari Singh Gour University , Sagar , Madhya Pradesh , India.
Govind P
GP
Agrawal
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003910:Dextranase / Q000737:chemistry; D003911:Dextrans; D016503:Drug Delivery Systems; D005079:Excipients; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008863:Microspheres; D010316:Particle Size; D011109:Polymethacrylic Acids; D051381:Rats; D012997:Solvents; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D003911:Dextrans; D005079:Excipients; D011109:Polymethacrylic Acids; D012997:Solvents; C038300:methylmethacrylate-methacrylic acid copolymer; D003910:Dextranase; D005472:Fluorouracil
Colon cancer; dextran microspheres; dextranase; organ distribution; pH-sensitive polymers