Patent GB-747914-A (GB)
Title: Improvements in or relating to pharmaceutical tablet or pellet and method of preparing the same
IPC: A61K9/20
Filed: 1953-09-17
Abstract: A timed-release pharmaceutical tablet comprises a uniform mass of non-time delay granules of a solid medicament, or a mixture of a liquid medicament and an inert solid filler, and time delay granules of said medicament dispersed in material resistant to rapid disintegration and slowly dispersible in the gastro-intestinal tract. The time delay granules are formed by liquefying the solid material resistant to rapid disintegration in the gastro-intestinal tract by heating or use of an organic solvent, dispersing the medicament in the liquified material, solidifying, powdering, wetting with a liquid granulating agent, screening and drying.  The non-time delay granules are present in amount about 25 to 100 per cent by weight of the time delay granules, the granules being about the same size.  Inert fillers may be added to the solid medicament but should not be in excess of 200 per cent by weight of the time delay material.  Where a liquid medicament is used, a filler is essential and is present in amount from about 40 to 60 per cent of the medicament-filler-time-delay mixture.  The time delay material is a fatty acid, alcohol or ester, alone or in admixture, and can be modified with a waxy material.  The fatty acid may have from 10 to 22 carbon atoms e.g. decenoic, stearic docosanoic, palmitic, lauric or myristic acid.  The fatty alcohol may have from 14 to 31 carbon atoms e.g. cetyl,, stearyl, myristyl, myricyl, arachyl, carnaubyl, ceryl. The esters may be mono-, di-, or tri-glyceryl esters of fatty acids having from 10 to 22 carbon atoms e.g. glyceryl monostearate, di-stearate, tri-stearate, glyceryl monopalmitate dipalmitate, tripalmitate, glyceryl monolaurate, dilaurate, trilaurate, glyceryl monodoconosoate, didocosonoate, tridocosanoate, glyceryl monocaprate, dicaprate, tricaprate, glyceryl monomyristate, dimyristate, trimyristate, glyceryl mono-decenoate, didecenoate, tridecenoate. The modifying wax material is an ester containing 24 to 62 carbon atoms of a fatty acid containing 12 to 31 carbon atoms and a fatty alcohol containing 12 to 31 carbon atoms e.g. myricyl palmitate, beeswax, cetyl palmitate, spermacetic wax, myricyl cerotate, carnauba wax, cetyl myristate, ceryl palmitate, ceryl cerotate, myricyl melissate, stearyl palmitate, stearyl myristate, lauryl laurate. Examples of the organic solvent are carbon tetrachloride, chloroform, trichloroethylene, petroleum ether, benzene, toluene, ethyl acetate, xylene, nitrobenzene, acetone, ether, carbon disulphide, methyl ethyl ketone, and alcohols such as methyl, ethyl, and isopropyl alcohol. The solid medicament may be a sympathomimatic agent e.g. amphetamine sulphate, dextro-amphetamine sulphate, racemic amphetamine sulphate, racemic or d-desoxyephedrine hydrochloride; and antispasmodic agent e.g. hyoscyamine, atropine, scopolamine hydrobromide; an antihistamine e.g. chloroprophenpyridamine maleate; a barbiturate e.g. phenobarbitol, barbital, armobarbital; an antibiotic e.g. procaine penicillin &c.  Amphetamine and N-phenoxyisopropyl-N-benzyl-b  chlorethylamine are exemplary of liquid medicaments which can be used.  Conventional fillers e.g. terra alba, lactose, sucrose, dextrose, sorbitol, and starch, can be added as desired.  The granulating solution comprises water (preferably 15 to 30 per cent, but no more than 50 per cent) and a monosaccharide (from 70 to 85 but not less than 50 per cent) of formula C6H12O6 e.g. dextrose, levulose, or a disaccharide of formula C12 H22O11, e.g. sucrose, lactose, maltose, or a polysaccharide e.g. dextrin, or mixtures thereof.  Alternatively, the granulating solution may contain water (75 to 90 per cent) and 10 to 25 per cent of gelatin, or a natural plant hydrocolloid e.g. acacia, agar, tragacanth, or an alginate e.g. sodium alginate, pectin, chondruo, or an aqueous solution of a hexahydric alcohol e.g. sorbitol, mannitol.