title: Mucoadhesive platforms for targeted delivery to the colon.
abstract: A novel platform system, comprising a mucoadhesive core and a rapid release carrier, was designed for targeted drug delivery to the colon. Prednisolone pellets containing different carbomers, including Carbopol 971P, Carbopol 974P and Polycarbophil AA-1, with or without organic acids, were produced by extrusion-spheronization. Mucoadhesive pellets were coated with a new enteric double-coating system, which dissolves at pH 7. This system comprises an inner layer of partially neutralized Eudragit S and buffer salt and an outer coating of standard Eudragit S. A single layer of standard Eudragit S was also applied for comparison purposes. Dissolution of the coated pellets was assessed in USP II apparatus in 0.1N HCl followed by Krebs bicarbonate buffer pH 7.4. Visualization of the coating dissolution process was performed by confocal laser scanning microscopy using fluorescent markers in both layers. The mucoadhesive properties of uncoated, single-coated and-double coated pellets were evaluated ex vivo on porcine colonic mucosa. Mucoadhesive pellets coated with a single layer of Eudragit S release its cargo after a lag time of 120 min in Krebs buffer. In contrast, drug release from the double-coated mucoadhesive pellets was significantly accelerated, starting at 75 min. In addition, the mucoadhesive properties of the core of the double coated pellets were higher than those from single-coated pellets after the core had been exposed to the buffer medium. This novel platform technology has the potential to target the colon and overcome the variability in transit and harmonize drug release and bioavailability.
authors.affiliation: Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Felipe J O
authors.initials: FJ
authors.lastname: Varum
authors.forename: Francisco
authors.initials: F
authors.lastname: Veiga
authors.forename: João S
authors.initials: JS
authors.lastname: Sousa
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Basit
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry*; D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D018613:Microscopy, Confocal; D008956:Models, Chemical; D011109:Polymethacrylic Acids / Q000737:chemistry; D011239:Prednisolone / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D013552:Swine; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005765:Gastrointestinal Agents; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C492577:carbopol 971P; C038300:methylmethacrylate-methacrylic acid copolymer; C030312:calcium polycarbophil; D011239:Prednisolone