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Extended release delivery system of metoprolol succinate using hot-melt extrusion: effect of release modifier on methacrylic acid copolymer

Abstract

The current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology. Either Eudragit®S100 and Eudragit®L100 alone or in combination with release modifying agent Polyox™ WSR 303 and Eudragit®L100-55 were processed to obtain complete and faster release. Metoprolol succinate with similar solubility parameters to polymer was dispersed in polymer matrix and was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Stability of drug after extrusion was confirmed by thermogravimetric analysis and high-performance liquid chromatography. Physical characterization method exhibited that the drug was homogeneously dispersed in non-crystalline state in Eudragit®L100-55-based formulations whereas in semi-crystalline state in Polyox™ WSR 303. The drug release percentage was below 3 and 40% in 0.1 N HCL with Eudragit®L100-55- and Polyox™ WSR 303-containing formulations, respectively, and exhibited pH-dependent dissolution properties. The drug-release mechanism was anomalous with Polyox™ WSR 303 formulations whereas diffusion through pore formation was obtained with Eudragit®L100-55. Both Eudragit®L100-55 and Polyox™ WSR 303 changed the release mechanism and kinetics of drug release from thermally processed dosage forms. The optimized stable formulation is similar to the marketed formulation with F2 value of 72.36. Thus, it can be concluded that HME was exploited as an effective process for the preparation of controlled release matrix system based on pH-dependent polymer matrices Eudragit®S100 and Eudragit®L100.

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Abbreviations

HME:

Hot-melt extrusion

MSN:

Metoprolol succinate

S100:

Eudragit®S100

L100:

Eudragit®L100

PEO303:

Polyox™ WSR 303

L100-55:

Eudragit®L100-55

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Acknowledgments

The author is thankful to UGC (SAP) for providing the research fellowship and Institute of Chemical Technology, ELITE status (Mumbai, India) for providing all facilities and guidance.

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Correspondence to Kiran P. Sawant.

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Sawant, K.P., Fule, R., Maniruzzaman, M. et al. Extended release delivery system of metoprolol succinate using hot-melt extrusion: effect of release modifier on methacrylic acid copolymer. Drug Deliv. and Transl. Res. 8, 1679–1693 (2018). https://doi.org/10.1007/s13346-018-0545-1

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  • DOI: https://doi.org/10.1007/s13346-018-0545-1

Keywords

  • Hot-melt extrusion
  • Metoprolol succinate
  • Eudragit®S100
  • Eudragit®L100
  • Eudragit®L100-55
  • Polyox™ WSR 303
  • Extended release
  • Release-modifying agent