title: A novel double-coating approach for improved pH-triggered delivery to the ileo-colonic region of the gastrointestinal tract.
abstract: Oral pH-responsive systems for drug delivery to the ileo-colonic region of the gastrointestinal tract show poor site specificity. Here, we describe a novel double-coating concept, based on the acrylic polymer EUDRAGIT S, which provides improved functionality for targeting performance. The coating system comprises an inner layer of partially neutralised EUDRAGIT S and buffer agent and an outer coat of standard EUDRAGIT S. Tablets containing prednisolone were coated with double-layer formulations with different inner coat compositions. A conventional single coating was also applied for comparison purposes. Dissolution of the coated tablets was assessed using USP II apparatus in 0.1M HCl for 2h followed by pH 7.4 physiological bicarbonate buffer (Krebs buffer), a medium which closely resembles the ionic composition and buffer capacity of the fluid in the distal small intestine. Following acid exposure, drug release from the EUDRAGIT S single-layer-coated tablets in pH 7.4 Krebs buffer was delayed for 120min. Release from the double-coated tablets was significantly faster compared to the single-coated tablets and was found to be affected by the pH and buffer capacity of the inner coat. The drug release lag time from the optimised double-coating formulation with an inner coat consisting of 10% KH(2)PO(4) (neutralisation pH of 8.0) was 40min. The accelerated coat dissolution and subsequent rapid drug release from the double-coating system can potentially overcome the limitations of conventional EUDRAGIT S coatings for ileo-colonic delivery.
authors.affiliation: Department of Pharmaceutics, The School of Pharmacy, University of London, London, UK.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Paloma
authors.initials: P
authors.lastname: Moreno
authors.forename: Abdul W
authors.initials: AW
authors.lastname: Basit
mesh_terms: D002021:Buffers; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D011239:Prednisolone / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D002021:Buffers; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D011239:Prednisolone