Patent GB-1116670-A (GB)
Title: Process for the manufacture of pharmaceutical preparations in bead form
IPC: A61K9/42
Filed: 1965-06-17
Abstract: A process for the manufacture of a pharmaceutical preparation in bead form comprises subjecting a mixture of a synthetic monomer and an organic medicament to bead polymerization, the mixture being capable when polymerized of yielding a physiologically tolerable polymeric material that is capable of being dissolved in or swollen by stomach and/or intestinal juices.  Preferred monomers comprise methyl methacrylate and mixtures of methacrylic acid and methyl methacrylate, methacrylic acid and divinylbenzene with or without methyl methacrylate, acrylic acid and methyl acrylate, vinyl acetate and crotonic acid, styrene and acrylic acid and/or maleic anhydride, vinyl methyl ether and maleic anhydride and/or fumaric acid and/or itaconic acid.  The polymerization mixture may contain conventional fillers, swelling agents, electrolytes, and surface active agents. The medicament may be coated in wax or fat, and synthetic resins that are insoluble in and not swollen by the stomach and/or intestinal juices may be included in the polymerization mixture.  Bead polymerization may be effected by dispersing the synthetic monomer-medicament mixture in a dispersion medium with which it is immiscible, e.g. water, in such a manner that beads having the desired degree of fineness are obtained, polymerization being carried out at room temperature or above generally with the aid of a catalyst, e.g. benzoyl peroxide, t-butyl hydroperoxide or azodiisobutyronitrile, and, optionally, an accelerator, e.g. a tertiary amine, an iron, manganese or cobalt compound, a sulphinic acid or a sulphite, and a dispersing agent, e.g. sodium polyacrylate or polyethylene glycol.  A preformed polymer may also be present, e.g. a vinylacetate/crotonic acid copolymer or an ethyl acrylate/t-butyl-acrylamide/acrylic acid copolymer.ALSO:A process for the manufacture of a pharmaceutical preparation in bead form comprises subjecting a mixture of a synthetic monomer and an organic medicament to bead polymerisation, the mixture being capable when polymerised of yielding a physiologically tolerable polymeric material that is capable of being dissolved in or swollen by stomach and/or intestinal juices.  Preferred monomers comprise methyl methacrylate and mixtures of methacrylic acid and methyl methacrylate, methyl methacrylate and divinyl benzene, acrylic acid and methyl acrylate, vinyl acetate and crotonic acid, styrene and acrylic acid and/or maleic anhydride, vinyl methyl ether and maleic acid anhydride and/or fumaric acid and/or itaconic acid.  Exemplified medicaments comprise 5 - (1-cyclohexenyl) - 5 - ethyl calcium barbiturate, acetyl para - phenetidine, 2 - ethyl - 2 - phenylglutarimide, papaverine, 4 - dimethylamino - 1 - phenyl - 2, 3 - dimethyl pyrozolone - 5, hydrocortisone, N - [6 - methoxy - 2 (methoxy - methyl) - 4 - pyrimidinyl] - sulphanilamide, and the sodium salt of 3 - acetylamino - 2,4,6 - triiodobenzoic acid.  The preparations may contain conventional fillers, swelling agents, electrolytes, and surface active agents.  The medicament may be coated in wax or fat, and synthetic resins that are insoluble in and not swollen by the stomach and/or intestinal juices may be included in the preparations.  Bead polymerisation may be effected by dispersing the medicament - synthetic monomer mixture in a dispersion medium with which it is imiscible in such a manner that beads having the desired degree of fineness are obtained, polymerisation being carried out at room temperature or above generally with the aid of a catalyst and an accelerator.  The preparations may be used in the form of granules, in capsules, in a liquid suspension medium, or in tablet form together with suitable adjuvants.