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

(2012) AAPS PHARMSCITECH. 13(4). p.1197-1211
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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.
Keywords
sustained release, solid state, tablet, WATER-SOLUBLE DRUGS, physicochemical properties, metoprolol, matrix, injection moulding, drug release, drug polymer interaction, acrylates, controlled release, SOLUBILITY PARAMETERS, SOLID DISPERSIONS, MELT EXTRUSION, POLYMERS, DELIVERY, PERMEABILITY, COPOLYMERS, RS, RL

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Citation

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Chicago
Quinten, Thomas, GP Andrews, Thomas De Beer, Lien Saerens, Wim Bouquet-Geerardyn, DS Jones, P Hornsby, Jean Paul Remon, and Chris Vervaet. 2012. “Preparation and Evaluation of Sustained-release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding.” Aaps Pharmscitech 13 (4): 1197–1211.
APA
Quinten, T., Andrews, G., De Beer, T., Saerens, L., Bouquet-Geerardyn, W., Jones, D., Hornsby, P., et al. (2012). Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding. AAPS PHARMSCITECH, 13(4), 1197–1211.
Vancouver
1.
Quinten T, Andrews G, De Beer T, Saerens L, Bouquet-Geerardyn W, Jones D, et al. Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding. AAPS PHARMSCITECH. 2012;13(4):1197–211.
MLA
Quinten, Thomas, GP Andrews, Thomas De Beer, et al. “Preparation and Evaluation of Sustained-release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding.” AAPS PHARMSCITECH 13.4 (2012): 1197–1211. Print.
@article{4142918,
  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.},
  author       = {Quinten, Thomas and Andrews, GP and De Beer, Thomas and Saerens, Lien and Bouquet-Geerardyn, Wim and Jones, DS and Hornsby, P and Remon, Jean Paul and Vervaet, Chris},
  issn         = {1530-9932},
  journal      = {AAPS PHARMSCITECH},
  keyword      = {sustained release,solid state,tablet,WATER-SOLUBLE DRUGS,physicochemical properties,metoprolol,matrix,injection moulding,drug release,drug polymer interaction,acrylates,controlled release,SOLUBILITY PARAMETERS,SOLID DISPERSIONS,MELT EXTRUSION,POLYMERS,DELIVERY,PERMEABILITY,COPOLYMERS,RS,RL},
  language     = {eng},
  number       = {4},
  pages        = {1197--1211},
  title        = {Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding},
  url          = {http://dx.doi.org/10.1208/s12249-012-9848-6},
  volume       = {13},
  year         = {2012},
}

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