A method to slow down the ionization-dependent release of risperidone loaded in a thermoresponsive poly(N-acryloyl glycinamide) hydrogel

Abstract

Poly(N-acryloyl glycinamide) polymers are soluble in hot aqueous media that gel rapidly on cooling. This gelatin-like behavior was previously compared with drug delivery requirements. Slow releases were demonstrated in vitro using different model molecules and macromolecules and in vivo using methylene blue. Risperidone is a weak basic drug sparingly soluble in water frequently used to treat patients suffering of schizophrenia. A standard risperidone-poly(N-acryloyl glycinamide) hydrogel formulation was selected from which the drug was allowed to release comparatively in buffered and non-buffered isotonic media at 37 °C under pseudo sink conditions. Linear release was observed in pH = 7.4 phosphate buffer whereas in buffer-free 0.15 M NaCl, the release was initially faster than in the buffer but became rapidly slower as the pH increased from 6.8 to 8.2. These features were related to the ionization-dependent solubility of risperidone. In order to minimize the ionization and thus the solubility of the drug inside the hydrogel despite outside buffering at 7.4, Mg(OH2), a sparingly soluble mineral base, was added to the standard formulation. This addition resulted in a c.a. threefold increase of the zero-order release duration. The method should be applicable to other sparingly soluble weakly basic drugs.

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Acknowledgements

Authors are indebted to CNRS, University Montpellier and CNRS for financial supports.

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Correspondence to Michel Vert.

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Boustta, M., Vert, M. A method to slow down the ionization-dependent release of risperidone loaded in a thermoresponsive poly(N-acryloyl glycinamide) hydrogel. Drug Deliv. and Transl. Res. 7, 460–464 (2017). https://doi.org/10.1007/s13346-017-0376-5

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Keywords

  • Poly(N-acryloyl glycinamide)
  • PNAGA
  • Sustained drug delivery
  • Gel-sol transition
  • UCST
  • Thermoresponsive hydrogel
  • Risperidone
  • Magnesium hydroxide
  • Hydrogel
  • Weak base