title: Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating.
abstract: The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage forms.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Department of Pharmaceutics and Biopharmaceutics, 1211 Geneva 4, Switzerland.
authors.forename: Cung An
authors.initials: CA
authors.lastname: Nguyen
authors.forename: Yvette Niamien
authors.initials: YN
authors.lastname: Konan-Kouakou
authors.forename: Eric
authors.initials: E
authors.lastname: Allémann
authors.forename: Eric
authors.initials: E
authors.lastname: Doelker
authors.forename: David
authors.initials: D
authors.lastname: Quintanar-Guerrero
authors.forename: Hatem
authors.initials: H
authors.lastname: Fessi
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
mesh_terms: D002626:Chemistry, Pharmaceutical; D008689:Methacrylates / Q000737:chemistry*; D008768:Methylmethacrylates; D049329:Nanostructures; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013608:Tablets, Enteric-Coated
chemical_list: D008689:Methacrylates; D008768:Methylmethacrylates; D011108:Polymers; D013501:Surface-Active Agents; D013608:Tablets, Enteric-Coated; C008384:methacrylic acid; C102808:Eudragit-E; C058665:Eudragit RL