Patent GB-1154317-A (GB)
Title: Oral Vehicle for Administering Drugs by Buccal Absorption
Inventor: RUSSELL HIGHAM STANLEY
IPC: A61K9/70
Filed: 1965-06-15
Abstract: 1,154,317. Oral shapes and forms. H. S. RUSSELL. 30 Aug., 1966 [15 June, 1965], No. 25162/65. Heading A5B. An oral vehicle for administering drugs by buccal absorption takes the form of a thin resilient body having a concave depression in at least one of its major surfaces, the body comprising a first layer at least part of which is soluble in and/or permeable to saliva and incorporates a drug absorbable by the oral mucous membranes, and a second layer having a different solubility and/or permeability and either containing a different drug or lacking any drug content the first layer may be formed of a soluble absorbable drug impregnated material such as an alginate, methyl cellulose, or preferably a glyco-gelatine, (gelatine having a suitable water content and plasticised with glycerol), and may be foamed or spongy. Alternatively this layer may consist of a matrix of porous spongy or foamed insoluble material, e.g. polyurethane, natural or synthetic rubber, polyvinyl chloride or sulphonated gelatine, impregnated with a mixture of the drug and a viscous settable liquid soluble in saliva, e.g. melted glyco-gelatin, which is then caused to set, the matrix being shaped if required during such setting. The second layer, which covers all the surfaces of the first layer except that having the depression, is either 1) more, or 2) less soluble and/or permeable than the first layer. In the case of 1) the second layer may be a sheet material, eg. treated paper, metal foil, plastics film, or an adherent coating, eg. of varnish, hard glyco-gelatine or sulphonated gelatine; for 2) a layer or coating of soft glyco-gelatine, with a high content of water and glycerine, is employed. Alternatively the two layers may be of the same material, with the second layer being thicker than the first. The vehicle may incorporate a third layer of insoluble material, eg. treated paper, metal foil, plastics film or varnish, either interposed between the first and second layer or as a coating on the outer surface of the second layer, and also may be provided with a protective backing on the concave face or both faces, which is to be removed before use of the vehicle; such a backing may connect several vehicles to form a strip. The vehicle is made 1) by coating the first layer with a melt or solution of the second layer material which is then set or dried. 2) by coating one side of a capsule of soluble permeable material with an impervious coating, the capsule containing a solution of the drug in a volatile solvent, and then drying the capsule, when the solvent migrates and evaporates through the uncoated capsule wall, depositing the drug therein, this wall ultimately collapsing inwards to give the required depression. The capsule may have an internal dividing partition. 3) A procedure similar to that of 2) may be employed using a capsule of homogenous composition but wherein the wall of one hemisphere is thicker than the opposite wall, preferential migration of the drug solution ocurring through the thinner wall, to give a vehicle having layers of the same composition but different thickness with the drug in the thinner layer. 4) The vehicle may be stamped out of a two-layered strip and then shaped to provide the depression. 5) The drug is incorporated into one side only of a preformed vehicle having one side protected by an impervious layer by exposing it to an aqueous or other solution of the drug which is absorbed by the unprotected side only, the vehicle afterwards being dried. Suitable drugs are: polypeptide and steroid hormones, e.g. vasopressin, insulin, oxytocin, heparin, testosterone, oestrpgens and progesterones: anaesthetics, e.g. hydrochlorides of lignocaine and diperodlon; sympathomimetic amines, e.g. adrenaline, nor-adrenaline, isoprenaline and amphetamine, and their antagonists, e.g. ergotamine, dibenylene; and various others such as morphine, glyceryl trinitrate, digitalin, barbiturates, acetyl choline, physistigmine, promethazine, atropine, hyoscine, amyl nitrate, caffeine, cyanocobalamin, para-amino-hippuric acid, and radio-isotopes. The vehicle may include a skin penetration promoter such as dimethyl sulphoxide.