Basic coating polymers for the colon-specific drug delivery in inflammatory bowel disease.
During acute attacks of inflammatory bowel disease, the luminal pH of the colon decreases significantly. This drop in pH can be exploited by developing coated dosage forms with acid-soluble coating polymers to achieve topical drug delivery to the colon. Two batches of minitablets, a conventional and a swellable formulation, were prepared by direct compression and coated with different amounts of either Eudragit E or AEA in a small coating pan. The release of the model drug dexamethasone from the coated tablets was measured spectrophotometrically at pH 2.0, 4.0, 5.0, and 6.8 and different stirring rates (100-200 rpm) to simulate the influence of pH and hydrodynamic stress on drug release. In general, lag times of drug release, determined as the time points of a 5% drug release, were longer with AEA-coated cores compared to those coated with Eudragit E, resulting from a lower polymer dissolution rate and water permeability of this film. In low pH media, drug release was dependent on the stirring rate because the onset of drug release is determined by the time required for dissolution of the basic polymer films. At pH 6.8, lag times from nonswelling tablets coated with Eudragit E, for which drug release only begins after complete erosion of the polymer film, are not significantly affected by hydrodynamic stress. Drug release from AEA-coated cores is determined by the slow drug diffusion through the polymer film. Lag times from tablets with swelling properties, for which drug release is induced by disruption of the basic polymer films due to water penetration and subsequent core swelling, are not significantly affected by hydrodynamic stress. Additional coating layers such as an intermediate hydroxypropylcellulose (HPC) layer and an enteric outer layer do not influence the lag times of drug release, nor does a 2-hr pretreatment of the entire dosage form in acidic media.
Leopold
C S
CS
Department of Pharmaceutical Technology, University of Leipzig, 04207 Leipzig, Germany. leopold@compuserve.com
Eikeler
D
D
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D011108:Polymers
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D011108:Polymers; D003907:Dexamethasone