Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding

AAPS PharmSciTech. 2012 Dec;13(4):1197-211. doi: 10.1208/s12249-012-9848-6. Epub 2012 Sep 11.

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.

MeSH terms

  • Acrylic Resins / chemistry
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Citrates / chemistry
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry*
  • Drug Compounding / methods
  • Drug Stability
  • Kinetics
  • Metoprolol / chemistry*
  • Plasticizers / chemistry
  • Polymers / chemistry
  • Porosity
  • Solubility
  • Tablets / chemistry*
  • Temperature

Substances

  • Acrylic Resins
  • Citrates
  • Delayed-Action Preparations
  • Drug Carriers
  • Plasticizers
  • Polymers
  • Tablets
  • Eudragit RS
  • Eudragit RL
  • ethyl citrate
  • Metoprolol