title: Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding.
abstract: Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Quinten
authors.forename: G P
authors.initials: GP
authors.lastname: Andrews
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.forename: L
authors.initials: L
authors.lastname: Saerens
authors.forename: W
authors.initials: W
authors.lastname: Bouquet
authors.forename: D S
authors.initials: DS
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Hornsby
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D007700:Kinetics; D008790:Metoprolol / Q000737:chemistry*; D010968:Plasticizers / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D002951:Citrates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010968:Plasticizers; D011108:Polymers; D013607:Tablets; C050528:Eudragit RS; C058665:Eudragit RL; C023001:ethyl citrate; D008790:Metoprolol