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Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

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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.

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium

    T. Quinten, W. Bouquet, J. P. Remon & C. Vervaet

  2. School of Pharmacy, Queen’s University Belfast, Lisburn Road 97, Belfast, BT9 7BL, UK

    G. P. Andrews & D. S. Jones

  3. Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium

    T. De Beer & L. Saerens

  4. School of Mechanical and Aerospace Engineering, Queen’s University Belfast, Stranmillis Road, Belfast, BT9 5AG, UK

    P. Hornsby

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  1. T. Quinten
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  2. G. P. Andrews
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  3. T. De Beer
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  4. L. Saerens
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  8. J. P. Remon
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  9. C. Vervaet
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Correspondence to C. Vervaet.

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Quinten, T., Andrews, G.P., De Beer, T. et al. Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding. AAPS PharmSciTech 13, 1197–1211 (2012). https://doi.org/10.1208/s12249-012-9848-6

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  • DOI: https://doi.org/10.1208/s12249-012-9848-6

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