Patent GB-833458-A (GB)
Title: Drug composition
IPC: A61K9/20
Filed: 1956-09-06
Abstract: A drug composition (see Group VI) for oral administration comprises a foraminous matrix of a solid synthetic resin in which particles of a solid drug are dispersed so that the drug is internally released over an extended time by leaching or diffusion.  The resins materials used in forming the permeable matrix are substantially physically inert to gastro-intestinal fluids and, in particular, are substantially insoluble therein; they are also non-toxic and can be ingested without danger.  It is preferred to use a plastic carrier which is not only substantially water-insoluble but which will be excreted substantially unchanged except for the loss of the drug therefrom. The resins suitable for use in this invention may be rubbery, glassy or crystalline but should be resistant to flow, sintering and "blocking".  They include:-  (1) polymers of acrylic esters, including solid homopolymers and copolymers of alkyl acrylates and methacrylates, such as methyl acrylate, methyl methacrylate, ethyl methacrylate, isopropyl acrylate, tert.-butyl acrylate, butyl methacrylate, hexyl methacrylate, dodecyl acrylate, dodecyl methacrylate, cetyl methacrylate, or stearyl acrylate, or of cycloalkyl or aralkyl acrylates or methacrylates, including cyclohexyl acrylate or methacrylate and benzyl acrylate or methacrylate, or of esters of acrylic or methacrylic acid and an ether alcohol such as ethoxyethanol, butoxyethanol, cyclohexoxyethanol, phenoxyethanol, or benzoxyethanol, and copolymers of one or more acrylic esters an another monovinylidene compound; (2) polymers of acrylonitrile and methacrylonitrile and copolymers based in substantial parts thereon together with another polymerizable monovinylidene compound;  (3) polymers of styrene, p-methylstyrene, or -methylstyrene, and copolymers with other monovinylidene compounds;  (4) polymers of ethylene and copolymers of ethylene and polymerizable monovinylidene compounds compatible therewith, butadiene polymers, polyfluoroethylenes;  (5) polyvinyl chloride and copolymers of vinyl chloride and vinyl carboxylates such as vinylacetate or vinyl propionate, and copolymers with other types of monovinylidene compounds;  (6) polyvinylidene chloride and copolymers of vinylidene chloride and other polymerizable monovinylidene compounds, such as acrylic esters enumerated above; (7) polyvinyl acetals, including polyvinyl formal, polyvinyl acetal, or polyvinyl butyral, and copolymers formed with other vinylidene compounds;  (8) polyvinyl esters of monocarboxylic acids, including acetic, propionic, butyric, lauric, or stearic, and copolymers with other types of monovinylidene compounds;  (9) linear condensation polymers of alkylene succinates or alkylene terephthalates, particularly ethylene succinate or terephthalate, alkylene adipamides, omega-hydroxyalkanoic acids, omega-aminocarboxylic acids, including such lactams as caprolactam.  There may also be used copolymers of one or more of the above monovinylidene monomers and a comonomer such as dimethyl itaconate, diethyl itaconate, a vinyl ether such as butyl vinyl ether, or ethoxyethyl vinyl ether, N-vinyl pyrrolidinone, acrylamide, N-methylacrylamide, N-ethylmethacrylamide, acrylic or methacrylic acid, and other polymerizable monovinylidene compounds.  There may also be used as comonomers small proportions of polyvinylidene compounds, particularly where there is a difference in the ease with which the several unsaturated linkages enter into polymerization.  There can then be formed a thermoplastic polymer into which a drug can be dispersed even though ultimately there is developed cross-linking.  The resins can be prepared by bulk, solution, suspension, or emulsion polymerization.  If the last method is used, the polymer may be coagulated into solid particles which can be readily mixed with a drug or a drug may be admixed before coagulation.ALSO:A drug composition suitable for oral administration comprises a foraminous matrix of a solid synthetic resin in which particles of a solid drug are dispersed so that the drug is internally released over an extended time by leaching or diffusion. Many examples of resins, including cellulose esters and ethers are given.  The drugs must be soluble to some extent in aqueous liquids, and drugs specified are p-aminobenzoic acid, ephedrine, mannitol hexanitrate, amphetamine, methamphetamine, erythromycin, penicillin, pentobarbital, atropine, belladonna, theophylline, sex hormones, hydantoins, trimethadione, Vitamins B and C, benzazoline and and toluidine blue O.  Methods of preparing the drug-in-plastic mass are given.  It is comminuted to a small particle size and preferably administered mixed with a pharmaceutical carrier.  The composition may be administered in tablet form.  An example describes tablets comprising 20% methamphetamine embedded in 80% of polyethylene, lactose, starch, water, talc, magnesium stearate.