Patent ID: 6911217

Claim:
A controlled-release bead comprising: (i) a core unit of a substantially water-soluble or water-swellable inert material; (ii) a first layer on the core unit of a substantially water-insoluble polymer; (iii) a second layer covering the first layer that contains an active ingredient, comprising compounds of the general formula wherein R 1 signifies hydrogen or methyl; R 2 , R 3 and R 4 independently signify hydrogen, methyl, methoxy, hydroxy, hydromethyl, carbamoyl, sulphamoyl or halogen; and X represents a tertiary amino group —NR 5 ,R 6 , wherein R 5 and R 6 signify non-aromatic hydrocarbyl groups, which may be the same or different, especially C 1-6 -alkyl or adamantyl, and which together contain at least three, preferably at least four carbon atoms, and each of which may carry a hydroxy substituent, and wherein R 5 and R 6 may form a ring together with the amine nitrogen, preferably a non-aromatic ring having no heteroatom other than the amine nitrogen, their salts with physiologically acceptable acids and, when the compounds can be in the form of optical isomers, the racemic mixture and the individual enantiomers, and (iv) a third layer of polymer on the second layer effective for the controlled release of the active ingredient, wherein said first layer is adapted to control water penetration into the core, and wherein the controlled-release bead provides a mean fluctuation index of said serum level of the active moiety or moieties that is not higher than about 2.0, said fluctuation index, FI, being defined as FI=(Cmax−Cmin)/AUCτ/τ, wherein Cmax and Cmin are the maximum and minimum concentrations, respectively, of the active moiety or moieties, AUCτ is the area under the serum concentration profile, and τ is the length of the dosage interval.