title: Controlled release of acidic drugs in compendial and physiological hydrogen carbonate buffer from polymer blend-coated oral solid dosage forms.
abstract: The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300 min. To simulate drug release from the mini tablets coated with RL/L55 blends in the gastrointestinal (GI) tract, drug release profiles in Hanks buffer pH 6.8 were recorded and compared with drug release profiles in compendial media. RL/L55 blend coatings showed increased drug permeability in Hanks buffer pH 6.8 compared to phosphate buffer pH 6.8 due to its higher ion concentration. However, drug release rates of acidic drugs were lower in Hanks buffer pH 6.8 because of the lower buffer capacity resulting in reduced drug solubility. Further dissolution tests were performed in Hanks buffer using pH sequences simulating the physiological pH conditions in the GI tract. Drug release from mini tablets coated with an RL/L55 blend (8:1) was insensitive to pH changes of the medium within the pH range of 5.8-7.5. It was concluded that coatings of RL/L55 blends show a high potential for application in coated oral drug delivery systems with a special focus on pH-independent release of acidic drugs.
authors.affiliation: University of Hamburg, Department of Chemistry, Division of Pharmaceutical Technology, Bundesstraße 45, 20146 Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wulff
authors.affiliation: Physiolution GmbH, Walther-Rathenau-Straße 49 a, 17489 Greifswald, Germany.
authors.forename: G-M
authors.initials: GM
authors.lastname: Rappen
authors.affiliation: University of Greifswald, Institute of Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Felix-Hausdorff-Straße 3, 17489 Greifswald, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Koziolek
authors.affiliation: Physiolution GmbH, Walther-Rathenau-Straße 49 a, 17489 Greifswald, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Garbacz
authors.affiliation: University of Hamburg, Department of Chemistry, Division of Pharmaceutical Technology, Bundesstraße 45, 20146 Hamburg, Germany. Electronic address: Claudia.Leopold@chemie.uni-hamburg.de.
authors.forename: C S
authors.initials: CS
authors.lastname: Leopold
mesh_terms: D000143:Acids / Q000737:chemistry*; D001639:Bicarbonates / Q000737:chemistry*; D002021:Buffers; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D000143:Acids; D001639:Bicarbonates; D002021:Buffers; D004364:Pharmaceutical Preparations; D011108:Polymers; D013607:Tablets
keywords: Enteric polymethacrylate; Hydrogen carbonate buffer; Interpolyelectrolyte complex; Polymer blend; Quaternary polymethacrylate; pH-independent drug release