title: Melt-Extruded Eudragit® FS-Based Granules for Colonic Drug Delivery.
abstract: The purpose of this study is to characterize the properties of Eudragit® FS-based granules prepared using melt extrusion process for colonic drug delivery. 5-Aminosalicylic acid (5-ASA), theophylline, and diclofenac sodium were used as the model compounds. Drug and polymer blends were melt-extruded into thin rods using a single screw extruder. Drugs were found to be dispersed as crystalline particles in the granules. A hammer mill was used to reduce the extrudate into 16-40 mesh granules, which were mixed with lactose and filled into hard gelatin capsules. Three-stage dissolution testing performed using USP paddle method was used to simulate drug release in gastrointestinal tract. In this study, melt extrusion has been demonstrated to be a suitable process to prepare granules for colonic delivery of 5-amino salicylic acid. At 30% drug loading, less than 25% 5-ASA was released from melt-extruded granules of 20-30 mesh in the first two stages (0.1 N hydrochloric acid solution and phosphate buffer pH 6.8) of the dissolution testing. All 5-ASA was released within 4 h when dissolution medium was switched to phosphate buffer pH 7.4. Drug loading, granule size, and microenvironment pH induced by the solubilized drug were identified as the key factors controlling drug release. Granules prepared with melt extrusion demonstrated lower porosity, smaller pore size, and higher physical strength than those prepared with conventional compression process. Eudragit® FS was found to be stable even when processed at 200°C.
authors.affiliation: Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA. feng.zhang@austin.utexas.edu.|College of Pharmacy, 2409 W. University Ave, PHR4.214, Austin, TX, 78712, USA. feng.zhang@austin.utexas.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003106:Colon / Q000187:drug effects*; D004008:Diclofenac / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D019804:Mesalamine / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000737:chemistry
chemical_list: D011108:Polymers; D011109:Polymethacrylic Acids; D004008:Diclofenac; C038300:methylmethacrylate-methacrylic acid copolymer; D019804:Mesalamine; D013806:Theophylline
keywords: 5-aminosalicylic acid; Eudragit® FS; colonic drug delivery; granulation; melt extrusion