title: 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.
authors.affiliation: Institute for Biomolecules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Faculty of Pharmacy, Montpellier University, 15 Avenue Charles Flahault, BP14491, 34093, Montpellier cedex 5, France.
authors.forename: Mahfoud
authors.initials: M
authors.lastname: Boustta
authors.affiliation: Institute for Biomolecules Max Mousseron (IBMM), UMR 5247, CNRS, ENSCM, Faculty of Pharmacy, Montpellier University, 15 Avenue Charles Flahault, BP14491, 34093, Montpellier cedex 5, France. vertm@univ-montp1.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Vert
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D014150:Antipsychotic Agents / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D018967:Risperidone / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D014150:Antipsychotic Agents; D020100:Hydrogels; C000591468:poly(N-acryloyl glycinamide); D018967:Risperidone
keywords: Gel-sol transition; Hydrogel; Magnesium hydroxide; PNAGA; Poly(N-acryloyl glycinamide); Risperidone; Sustained drug delivery; Thermoresponsive hydrogel; UCST; Weak base