title: Release characteristics of polyurethane tablets containing dicarboxylic acids as release modifiers - a case study with diprophylline.
abstract: The influence of several dicarboxylic acids on the release characteristics of polyurethane tablets with a high drug load was investigated. Mixtures of diprophylline (Dyph) and thermoplastic polyurethane (TPUR) (ratio: 50/50, 65/35 and 75/25 wt.%) were hot-melt extruded and injection molded with the addition of 1, 2.5, 5 and 10% wt.% dicarboxylic acid as release modifier. Incorporating malonic, succinic, maleic and glutaric acid in the TPUR matrices enhanced drug release, proportional to the dicarboxylic acid concentration in the formulation. No correlation was found between the water solubility, melting point, logP and pKa of the acids and their drug release modifying capacity. Succinic and maleic acid had the highest drug release modifying capacity which was linked to more intense molecular interactions with Dyph. A structural fit between the primary and secondary alcohol of Dyph and both carboxylic groups of the acids was at the origin of this enhanced interaction.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Claeys
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Sander
authors.initials: S
authors.lastname: De Bruyn
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutical Analysis, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D003998:Dicarboxylic Acids / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D004400:Dyphylline / Q000008:administration & dosage* / Q000737:chemistry; D015394:Molecular Structure; D011140:Polyurethanes / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D003998:Dicarboxylic Acids; D004337:Drug Carriers; D011140:Polyurethanes; D013607:Tablets; D004400:Dyphylline; C062725:Tecoflex
keywords: Drug delivery systems; Extrusion; Polymers; Release modifier