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Drug release mechanisms from Kollicoat SR:Eudragit NE coated pellets

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Author

  • Y. Cuppok
  • S. Muschert
  • Mariagrazia Marucci
  • J. Hjaertstam
  • F. Siepmann
  • Anders Axelsson
  • J. Siepmann

Summary, in English

Thin, free films based on Kollicoat SR:Eudragit NE blends were prepared by casting or spraying aqueous dispersions of these polymers, and were thoroughly characterized with respect to their water uptake behavior, water permeability, dry mass loss kinetics, mechanical properties and drug release patterns. A mechanistic mathematical model based on Fick's law of diffusion was used to quantify the experimentally measured release of metoprolol succinate from various types of systems. With increasing Eudragit NE content the films became more hydrophobic, resulting in decreased water permeability as well as water uptake rates and extents. In addition, the dry mass loss upon exposure to the release medium decreased. Consequently, the films' permeability for the drug decreased. Importantly, metoprolol succinate release from thin films was mainly controlled by pure diffusion, allowing for the determination of the apparent diffusion coefficient of the drug in the different polymeric systems. Knowing these values, drug release from coated pellets could be quantitatively predicted, assuming intact film coatings throughout the observation period. Comparison with independent experimental results showed that crack formation set on very rapidly in the polymeric membranes upon exposure to the release medium in the case of sugar starter cores, irrespective of the polymer:polymer blend ratio and investigated coating level. In contrast, the onset of crack formation was delayed as a function of the blend ratio and coating thickness in the case of microcrystalline cellulose starter cores, attracting less water into the pellets core. The obtained new insight into the underlying drug release mechanisms can be very helpful during device optimization and improve the safety of this type of advanced drug delivery systems. (C) 2011 Elsevier B.V. All rights reserved.

Publishing year

2011

Language

English

Pages

30-37

Publication/Series

International Journal of Pharmaceutics

Volume

409

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Chemical Engineering

Keywords

  • Drug release mechanism
  • Mathematical modeling
  • Coated pellets
  • Polymer
  • blends
  • Kollicoat SR
  • Eudragit NE

Status

Published

ISBN/ISSN/Other

  • ISSN: 1873-3476