IL30165A

IL30165A - Multi-layered medicinal tablets

Info

Publication number: IL30165A
Application number: IL30165A
Authority: IL
Original assignee: Dausse Lab
Priority date: 1967-06-15
Filing date: 1968-06-12
Publication date: 1973-04-30
Also published as: FR1545612A; DE1767765A1; BE716530A; GB1233055A; NL151902B; NL6808312A; SU458966A3; IT954035B; IL30165A0; ES355054A1; LU56264A1

Description

ηηπκ maav m^pa m*nDim m»Vae Multi-layered medicinal tablets LES MBORATOIRES DAUSSE C, 28474 30165/4 ^ This Invention relates to the production of multilayered medicinal .tablets.

It has already been propose to make or pharmaceutical use tablets containing a nucleus and one or more peripheral layers, in particular so that two active substances can be kept apart until the tablet is absorbed in the organism. It is also known that the exclplents of tablets may consist of, or contain, one or more materials capable or retarding the liberation of the active substance which thus becomes available gradually.

Composite medicinal tablets containing retarding ingredients in some of their parts are known.

Some of them comprise a nucleus and one or more superposed layers surrounding the nucleus. The accepted technique of making them consist in coating the nucleus wit th surrounding layers by a casting operation.

Xt has surprisingly been found,in accordance wit this invention, that retarding tablets in which , bot the nucleus and the surrounding layers are produced by compression, provide a much more regular and controllable release of the medicine and that, if desired, the release may be made more protracted, than with tablets made by conventional techniques.

In the tablets according to the invention, the retarding ingredients may be conventional ones, e.g. gum-lac, stearic acid or its salts and esters , especially magnesium stearate, wlt ewax, vegetable waxes such as Carnauba wax, polyethylen glycol, e.g. of molecular weight of about 4000, sodium dioctyl sulphosuccinate, cellulose acetophthalate, optionally plaaticised with a phthalic ester, such as ethyl phthalate or butyl phthalate, or 'th like.

Each Mretardede' part of the tablet may, if desired, contain more tha one retarding ingredient, and the "retarded" parts may be medicated with the same or different active substances. mendment ¾e-pafeesuree-t»ed-4n-pred«ie4ng-i*»st-the nder Secion 65. n«eieee-«d«hen- e~«*ue»ew 30165/5 The invention Is illustrated b the following Examples.

Example 1 Nucleus (0.110 g) Papaverine hydrochloride 0.034 g Ethoxazorutin 0,025 g Ascorbio acid 0.025 g , Gum-lac (in alcohol of 95# 0.015 g strength) Magnesium etearate ' 0.010 g Talc 0.001 g The ascorbio acid is granulated with 3# of its weight of the gum-lao in alooholic rotation. The balanoe of that solution is used for the granulation of the remaining ingredients. The two granulates are air-dried, then mixed and compressed under a pressure of * 7 tons (metric)/cm'2.

First layer (0.120 g¾ Papaverine hydrochloride 0.033 g Ethoxazorutin 0.025 g Ascorbio acid 0.025 g Gum-lac · 0.0075 g · Magnesium etearate : 0.006 g Gum arable powder 0.0235 β The Ingredients are pretreated and mixed in the same manner as for the nucleus but the amount of gum-lac used for the granulation of the ascorbic acid is 0,15% by weight.. The mixture is appliedjo the nucleus and compressed on to the latter under a pressure of 5 tons/cm^.

Second layer (0.250 g) Papaverine hydrochloride 0.033 g Ethoxazorutin 0.025 g Ascorbic acid 0.025 g Gum-lac 0.00375 g Magnesium stearate 0.010 g Powdered gum arable 0.100 g Icing sugar 0.05325 g The procedure is the same as for the first layer, the amount of gum-lac used for granulating the ascorbic acid is 0.1$ by weight, the compression is effected at 4 tons/cm · Outer layer (0.320 a) Powdered gum arable trace Talc 0.050 g Crystallised sucrose 0.270 g Tartrazine trace Carnauba wax trace This layer is produced in a conventional manner.

The weight of the tablet thus produced is 0.800 g.

In the dog, whose metabolism is more active than that of man, the presence of the papaverine in the blood can be detected 30 minutes after the ingestion of such tablets, and the concentration remains constant for more than six hours afterwards.

Example 2 Nucleus Active substance 0.0025 g Powdered sucrose 0.029 g Powdered gum arabic 0.025 g Talc 0.006 g Stearic acid 0,012 g Cetyl alcohol 0.002 g Gum-lac (as a 50$ solution 0,0035 g in 9 $ alcohol) The ingredients are mixed, the mixture is passed through a granulator, the granules are dried on screens and sieved through a No* 30 sieve. The mixture is then made into a tablet nucleus weighing 0.0800 g on a Bicota ¾ 2 machine using turrevl/4, under a pressure of 6 tons/cm .

Firs layer Active substance 0.0025 g powdered sucrose 0.0535 g Powdered gum arabic 0.030 g Talc 0.009 g Stearic acid 0.017 g Cetyl alcohol 0.003 g .

These ingredients are mixed, the mixture is passed through a granulator, the granulars are dried on a screen and sieved through sieve No. 30. The layer is then applied to the nucleus in a proportion of 0.100 g to 0.0800 g of nucleus, by means of a Bicota machine with 2 second turret 010/32, under a pressure of 4 tons/cm · Second coating Active substance 0.0025 g Powdered sucrose 0.0765 g Powdered gum arabic 0.075 g Talc 0.014 g Stearic acid 0.022 g Cetyl alcohol 0.005 g Guru-lac (used as a 50 solution in 9 # alcohol) 0.005 g The ingredients are mixed, the mixture is passed through a granulator, the granules are dried on a screen and sieved through ¾ Wo. 30 sieve. The nucleus carrying the first layer is then coated with 0.2 g of this mixture 0,13/32 in a Bicota machine with a third turret/under a pressure of 2 tons/cm".

The tablets thus obtained, weighing 0.380 g, are. then enrobed in a conventional manner with a sugar-coating to produce tablets weighing 0.650 g each* Example 3 Nucleus Active substance 80 mg Talc 10 mg Glyceryl monostearate 20 mg The glyceryl stearate Is dissolved in alcohol on a water oath and the mixture is granulated. The active substance and the talc are mixed with the solution which is partially dried, screened, and then completely diied.

The nuclei are made in a Bicota tabletting machine using 2 the first turret 01/4, under a pressure of 4 tons/cm · First coating Active substance 100 mg Calcium carbonate 20 mg Wool fat 20 mg Powdered gum arable 20 mg 95$ aqueous alcohol and water ¾.β.

Total 160 mg The active substance, calcium carbonate and powdered gum arable are mixed* The wool fat is dispersed in hot alcohol and the mixture of powder is mixed with the solution. ¾e mixture is dried, ground in a mortar and admixed with enough water to allow the mixture to be granulated. The coating is applied to the nuclei in a Bicota machine using a second turret 03/8» under 2 a pressure of 3 tons/cm · Second coating Active substance 120 mg Kaolin 80 mg Lanolin. 30 mg Gum arable 40 mg Alcohol and water q.s.

Total 270 mg ,.

The same procedure is followed as with the first layer, using on the Bicota machine the third turret 2 0 15/32 under a pressure of 2 tons/cm · Example Nucleus Active substance 70 mg Talc 20 mg Stearic acid 10 mg Gum-lac 15 mg Ethyl phthalate 3 mg 955^ alcohol q. s· Total 118 mg The stearic acid and talc are mixed hot, the mixture is allowed to cool and finely ground. The aotlve substance is added and the well-mixed mixture is granulated with a solution of the gum-lac and ethyl phthalate in alcohol. The mixture is then ground and made into nuclei on a Bicota machine using a first turret 01/4, under a 2 pressure of 5 tons/cm * First coating Active substance 80 mg Icing sugar 10 mg Powdered gum arable 10 mg Stearic acid 15 mg Gum-lac 10 mg ¾hyl phthalate 2 mg 9 alcohol ¾.s.

Total 127 mg The same procedure is followed as in the production of the nucleuo and a coating is applied to the latter on the Bicota machine using the sedond turret 2 03/8 under a pressure of 4 tons/cm .

Second coating Active substance Icing sugar Powdered gum arable Gum-lac Stearic acid Talc Alcohol and water Total The same procedure is followed as with the first coating* The solids are mixed with gum-lac and dilute alcohol, dried and powdered. The coating is applied to the nuclei carrying the first coating on the Bicota machine using the third turret 015/32 under a pressure of 3 tons/cm* This invention relates to the production of multilayered medicinal tablets.

It has already been proposed to make for pharmaceutical use tablets containing a nucleus and one or more peripheral layers, in particular so that two active substances oan be kept apart until the tablet is absorbed in the organism. It is. lso known that the exciplents of tablets may consist of, or contain, one or more materials capable of retarding the liberation of the active substance which thus becomes available gradually.

The present invention has the object to provide tablets from which the active substances are liberated in a particularly protracted manner.

The invention consists in a tablet comprising a nucleus and at least two outer layers in which the nucleus and the outer layers contain the active ingredient and a retarding Ingredient for delaying the release of the active ingredient from the nucleus and the outer layers after administration of the tablet, the nature and proportion of the retarding ingredient being such that the rates of release of the active ingredient are different in the nucleus and each layer and increase from the nucleus outwards, characterized in that both the nucleus and the outer layers are produced by compression, that the nucleus is more highly compressed than the outer layers, and that each layer is more highly compressed than the next outer layer, if any,.

Composite medicinal tablets containing retarding ingredients in some of their ports are known. Some of them comprise a nucleus and one or more superposed layers surrounding the nucleus. The accepted technique of making them consist in coating the nucleus with th© surrounding layers by a casting operation.

It has surprisingly been found, in accordance with this invention, that retarding tablets in which both the nucleus and the surrounding layers are produced by compression, provided a much more regular and controllable release o the medicine and that* if desired, the release may be made more protracted, than with tablets made 'by conventional techniques.

In the tablets according to the invention, the retarding ingredients may be conventional ones, e.g. gum-lac, stearic acid or its salts and esters, especially magnesium stearate, white wax, vegetable waxes such as Camauba wax, polyethylene glycol, e.g. of molecular weight of about 4000, 3odium dioctyl sulphosuccinate , cellulose acetophthalate, optionally plasticised with a phthalic ester, such as ethyl phthalate or butyl phthalate, or the like.

Each "retarded" part of the tablet may, if desired, contain more than one retarding ingredient, and the "retarded" parts may be medicated with the same or different active substances* The pressures used in producing first the nucleus and then the surrounding layers may be different. 30165/5

Claims

CLAIMS 1. A tablet comprising a nucleus and at least two oute layers in which the nucleus and the outer layers contain the at least one active ingredient selected from the group of papaverine hydrochloride., ethoxazorutin and ascorbic acid and a at least one retarding ingredient for delaying the release of the active ingredient(s) from the nucleus and the outer layers a ter administration of the tablet, the nature and proportion of the retarding ingredien being such that the rates of release of the active ingredient are di ferent in the nucleus and each layer and increase from the nucleus outwards, characterized active ingredient or retarding ingredient, 5, Tablets according to Claim 1 substantially as 30165/4 Claims

1. A tablet comprising a nucleus and at least two outer layers in which the nucleus and the outer layers contain the active ingredient and a retarding ingredient for delaying the release of the active ingredient from the nucleus and the outer layers after administration of the tablet, the nature and proportion of the retarding ingredient being such that the rates of release of the active ingredient are different in the nucleus and each layer and increase from the nucleus outwards, characterized in that both the nucleus and the outer layers are produced by compression, that the nucleus is more highly compressed than the outer layers, and that each layer is more highly compressed than the next outer layer, if any.

2. A tablet according to Claim 1, in which the retarding ingredient is gum-lac, stearic acid or a salt or ester thereof, white wax, Carnauba wax, a polyethylene glycol, sodium dioctylsuphosuccinate, or cellulose acetophthalate·

3. A tablet according to Claims 1 or 2, in which the active ingredient comprises papaverine hydrochloride.

4. A tablet according to any one of Claims 1 to 3» which also comprises an outermost coating containing no active ingredient or retarding ingredient.

5. Tablets according to Claim 1 substantially as described. PARTNERS