title: Comparison of metoprolol tartrate multiple-unit lipid matrix systems produced by different technologies.
abstract: The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices. Prilling tended to be susceptible to increased melt viscosity. Direct compression was not applicable for mini-matrix production due to poor powder flow. In general MPT release from all matrices was affected by its loading and the size of the units/particles. Processing of GB-MPT mixtures by different techniques did not lead to different drug release rates and patterns, while in case of GPS differently obtained matrices provided diverse MPT release outcomes. Matrices based on GB tended to have higher porosity compared to ones composed of GPS and thus most of the GB-based formulations showed faster drug delivery. FT-IR analysis revealed no interactions between primary components used for matrix production and Raman mapping outlined uniform MPT distribution throughout the units. DSC and X-ray studies revealed significant changes in the crystallinity of glycerides after storage under room conditions (GPS samples) and at increased temperature (GB and GPS samples), which was correlated to the changes seen in drug release rate and pattern after storage. Media composition in general tended to insignificantly affect GB matrices, while in case of GPS matrices increasing the pH and presence of biorelevant compounds induced faster drug release.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Aleksovski
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Van Bockstal
authors.affiliation: Department of Biopharmacy and Pharmacokinetics, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Robert
authors.initials: R
authors.lastname: Roškar
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Eötvös 6, 6720 Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Sovány
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Eötvös 6, 6720 Szeged, Hungary.
authors.forename: Géza
authors.initials: G
authors.lastname: Regdon
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: rok.dreu@ffa.uni-lj.si.
authors.forename: Rok
authors.initials: R
authors.lastname: Dreu
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004345:Drug Industry; D065546:Drug Liberation; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008790:Metoprolol / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D005989:Glycerides; D008055:Lipids; D008790:Metoprolol
keywords: Compression; Extended release; Hot-melt extrusion; Metoprolol tartrate; Mixed glycerides; Prilling