title: Preparation and evaluation of colon adhesive pellets of 5-aminosalicylic acid.
abstract: Oral modified-release delivery systems, such as bio-adhesive one, enable drug delivery to affected regions and minimize the side effects by reducing the systemic absorption. Our aim was to develop colon adhesive pellets of 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis. The core of the pellet was formulated from bioadhesive agents, Carbomer 940 and hydroxypropyl cellulose (HPC), by extrusion/spheronization method and coated with Surelease(®) as inner layer for waterproof and with Eudragit(®) S100 as outer layer for pH control. The rat model of ulcerative colitis was used to evaluate the efficiency of our loaded pellets as a drug carrier. Microcrystalline cellulose 101 (PH 301) was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as (1:1) to achieve high bioadhesion. When the amount of Surelease(®) was from 16% to 20% and of Eudragit(®) S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in the artificial gastric fluid (pH 1.0) within 2h and less than 10% was released in phosphate buffer (pH 6.0) within 2h whereas complete dissolution was observed in colonic fluid of pH 7.4 for 20 h. The animal experiment showed that 5-ASA loaded colon adhesive pellets had optimal therapeutic effect. We showed a novel approach to prepare effective bioadhesive pellets as colon targeted drug delivery system.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sun_minjie@163.com.
authors.forename: Minjie
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Qiao
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, Omudrman Islamic University, Khartoum, 00249, Sudan.
authors.forename: Eltayeb Suliman
authors.initials: ES
authors.lastname: Elamin
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D004337:Drug Carriers; D005079:Excipients; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; D019804:Mesalamine; C006903:carbopol 940; C013517:ethyl cellulose; D014302:Trinitrobenzenesulfonic Acid; D002482:Cellulose; C008079:hydroxypropylcellulose; C109691:microcrystalline cellulose
keywords: 5-Aminosalicylic acid; Bioadhesion; Colon-specific delivery; Extrusion spheronization; Pharmacodynamics