title: Extended release of flurbiprofen from tromethamine-buffered HPMC hydrophilic matrix tablets.
abstract: The pH-dependent solubility of a drug can lead to pH-dependent drug release from hydrophilic matrix tablets. Adding buffer salts to the formulation to attempt to mitigate this can impair matrix hydration and negatively impact drug release. An evaluation of the buffering of hydrophilic matrix tablets containing a pH-dependent solubility weak acid drug (flurbiprofen), identified as possessing a deleterious effect on hydroxypropyl methylcellulose (HPMC) solubility, swelling and gelation, with respect to drug dissolution and the characteristics of the hydrophilic matrix gel layer in the presence of tromethamine as a buffer was undertaken. The inclusion of tromethamine as an alkalizing agent afforded pH-independent flurbiprofen release from matrices based on both HPMC 2910 (E series) and 2208 (K series), while concomitantly decreasing the apparent critical effect on dissolution mediated by this drug with respect to the early pseudo-gel layer formation and functionality. Drug release profiles were unaffected by matrix pH-changes resulting from loss of tromethamine over time, suggesting that HPMC inhibited precipitation of drug from supersaturated solution in the hydrated matrix. We propose that facilitation of diffusion-based release of potentially deleterious drugs in hydrophilic matrices may be achieved through judicious selection of a buffering species.
authors.affiliation: a Department of Pharmacy , University of Nottingham , Nottingham , UK.|b Commercial Trade Channels , Merck Sharp and Dohme Ltd , Hoddesdon , UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Pygall
authors.affiliation: a Department of Pharmacy , University of Nottingham , Nottingham , UK.|c SarKon Ltd , Llanelli , UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kujawinski
authors.affiliation: d Drug Product Science and Technology , Bristol-Myers Squibb Pharmaceuticals Ltd , Moreton , UK.|e Department of Pharmacy , University of Huddersfield , Huddersfield, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Timmins
authors.affiliation: a Department of Pharmacy , University of Nottingham , Nottingham , UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Melia
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D005480:Flurbiprofen / Q000737:chemistry / Q000493:pharmacokinetics*; D065347:Hypromellose Derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D014325:Tromethamine / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D014325:Tromethamine; D065347:Hypromellose Derivatives; D005480:Flurbiprofen
keywords: Drug–polymer interaction; HPMC; flurbiprofen; pH-independent dissolution; tromethamine