Patent GB-638284-A (GB)
Title: Improvements in or relating to enteric capsules
IPC: A61K9/48
Filed: 1947-02-14
Abstract: A composition suitable for the preparation of hard-shell enteric medicinal capsules comprises gelatin, an alkali metal carboxylate salt of the acid form of a polycarboxylic acid partial ester of a cellulose ester of an aliphatic monocarboxylic acid containing 1 to 4 carbon atoms and from 0 to 5 per cent of a plasticizer (based on the weight of the dry gelatin) such as glycerin or propylene glycol. Colouring agents such as Erythrosene, Fast Green, Brilliant Blue, Amaranth, Magenta and Tartrazine may also be present.  Preferably, 4 to 9 parts by weight of gelatin are employed to 1 part of the unneutralized cellulose derivative.  The cellulose derivatives prepared, e.g. by the methods disclosed in U.S.A.  Specifications 2,093,462, 2,093,464 and 2,126,460 are alkali metal salts of polycarboxylic acid (e.g. phthalic, succinic, maleic) partial esters of cellulose esters of aliphatic monobasic acids containing 1 to 4 carbon atoms, e.g. cellulose-acetate-phthalate and cellulose-propionate-phthalate.  The unneutralized cellulose derivative may contain 5 to 25 per cent, but preferably 8 to 15 per cent, free carboxyl.  In the example, a small quantity of glycerol oleate is added to prevent frothing when dissolving the cellulose-acetate-phthalate in aqueous sodium carbonate at a pH of 5.9.  This solution and the gelatin, previously soaked in water, is heated at 120 DEG  F. for 4 to 12 hours and the half capsules are then formed on lubricated dipping pins using, e.g. automatic machines such as are described in U.S.A.  Specification 1,787,777. Other alkalis such as sodium carbonate, potassium carbonate, sodium hydroxide, trisodium phosphate, sodium perborate, potassium hydroxide, lithium hydroxide and lithium carbonate may be used for forming the alkali metal salt of the cellulose partial ester. Specification 526,276 and 610,538 are referred to.ALSO:A hard-shell enteric capsule is prepared by mixing an aqueous solution of gelatine with an aqueous solution of an alkali metal salt of a polycarboxylic acid partial ester of a cellulose ester of a lower aliphatic carboxylic acid containing 1 to 4 carbon atoms to obtain a viscous homogeneous aqueous solution, forming a portion of said viscous solution by means of a mould into the shape of a half capsule at a temperature of over 100 DEG  F, cooling at a temperature of less than 65 DEG  F, drying with humidified air and joining said capsule half with a similar capsule half having a diameter such that the two units telescope into one another.  The capsule halves may be sealed by an encircling band formed of material similar to that of the capsule, gelatin or other resinous sealing material.  Automatic machines such as are described in U.S.A.  Specification 1,787,777 may be used for forming the capsule halves using the gelatin/cellulose ester salt admixtures at 95 to 125 DEG  F.  In the example, the half capsules are formed on lubricated dipping fins.ALSO:A hard-shell enteric capsule is prepared by mixing an aqueous solution of gelatin with an aqueous solution of an alkali metal salt of a polycarboxylic acid partial ester of a cellulose ester of a lower aliphatic carboxylic acid containing 1 to 4 carbon atoms to obtain a viscous homogeneous aqueous solution, forming a portion of said viscous solution by means of a mould into the shape of a half capsule at a temperature of over 100 DEG F, cooling at a temperature of less than 65 DEG F, drying with de-humidified air and joining said capsule half with a similar capsule half having a diameter such that the two units telescope into one another.  The capsule halves may be sealed by an encircling band formed of material similar to that of the capsule, gelatin or other resinous sealing material.  Automatic machines such as are described in U.S.A. Specification 1,787,777 may be used for forming the capsules casing the gelatin/cellulose ester salt admixtures at 95-125 DEG F.  The capsule walls, which thus consist of a homogeneous dispersion of the enteric cellulose salt in gelatin, may contain up to 5 per cent (based on the weight of the dry gelatin) of a plasticizer such as glycerin or propylene glycol.  Colouring agents such as Erythrosene, Fast Green, Brilliant Blue, Amaranth, Magenta and Tartrazine may also be present.  Preferably, 4 to 9 parts by weight of gelatin are employed to 1 part of unneutralized cellulose derivative.  The cellulose derivatives (prepared by methods such as are described in U.S.A. 2,093,462, 2,093,464 and 2,126,460) are alkali metal salts of polycarboxylic acid (e.g., phthalic, succinic, maleic) partial esters of cellulose esters of lower aliphatic monobasic acids containing 1 to 4 carbon atoms. They may be prepared by the action of a polycarboxylic acid anhydride on a cellulose ester which contains free hydroxyls in the cellulose part of the molecule, e.g., cellulose acetate, cellulose propionate, cellulose acetate-propionate, cellulose butyrate, and they have at least one free, unesterified carboxylic acid group present in the polybasic acid portion of the molecule, e.g., cellulose-acetate-phthalate and cellulose propionate phthalate.  An aqueous solution of the salt may be obtained by adding the cellulose acid derivative to an aqueous solution of an alkali such as sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide, trisodium phosphate, sodium perborate, potassium hydroxide, lithium hydroxide and lithium carbonate.  The unneutralized cellulose derivative may contain 5 to 25 per cent free carboxyl but preferably 8 to 15 per cent.  In the example, a small quantity of glycerol oleate is added to prevent frothing when dissolving the cellulose acetate phthalate in aqueous sodium carbonate to a pH of 5.9.  This solution and the gelatin, previously soaked in water, is heated at 120 DEG F for 4 to 12 hours and the half capsules are then formed on lubricated dippin pins. Specifications 526,276 and 610,538 also are referred to.