DE1767765A1 - Process for the production of multilayer tablets - Google Patents

Description

Dr. Walter Beil
rsc ..iO € ppener

Dr. F ^ CNv B ^ l

Fran ":! I :: -: a. M.-Höchst

Adelenstrasse 58 - Tel. 3010 24

Our no.14.873

Les Laboratoires Daussa Paris, France

Process for the production of multi-dose tablets.

For pharmaceutical use tablets have already been proposed which consist of a core and several peripheral layers, so that in particular two active substances can be kept separate from one another until the tablet M dissolves in the organism.

It is also known to be used in the manufacture of Tablets incorporate binder components that consist of one or more materials, which delay dissolution, which gradually releases the active ingredient.

The present invention relates to a method for the manufacture of tablets, which is a particularly progressive Release of the active ingredient (s) that they contain bind to ensure. "V

2098U / 1613

The by means of the multilayer tablets produced according to the invention The delay in the resolution caused is expressed in a mode of action that differs from that of those is how it is achieved when each layer with the same composition on its own as a tablet is taken.

According to a particular embodiment of the present Invention one works in the production of tablets from several structural components, i.e. tablets with one Core surrounded by one or more layers in one or more of these constituents retardants, depending on the amount in which they are present and / or differ due to their nature, so that these two components have different dissolution times.

As the retarding substances, materials which have already been proposed as such can be used are, in particular rubber, especially lacquer, stearic acid, its salt and isers, such as in particular magnesium tearate, white guard, vegetable waxes such as Gar naubawaohs, Polyalkylene glycols, especially polyethylene glycols, like * .B, polyethylene glycol 4000, sodium dioctylsulfosuooinate, Oellulose acetophthalate, possibly in combination with a phthalic acid ester such as ethyl or butyl phthalate, this list is only given for the purpose of illustration «without representing any restriction.

Any element (core or layer) of the tablet that

If you want to gradually dissolve, you can have one or more retarding Containing ingredients, and the elements containing the same can contain the same active ingredient or have various active ingredients.

A simple case is that a nucleus has a retarding component and a peripheral layer a lesser amount of the retarding component, for example half, contains.

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Finally, it is possible to press the elements to different degrees, especially the core strongest pressure and to produce the layer or layers under a lower pressure or gradually decreasing pressure, especially when the retarding ingredient is a resin such as Gummilack.

example 1

A typical example of a tablet in which the essential delaying ingredient is gummilack is given below.

Papaverine chlorohydrate

Ethoxazorutin Ascorbic Acid Lacquer Magnesium Stearate talc

Papaverine chlorohydrate

Ethoxazorutin ascorbic acid Gum Lacquer Magnesium Stearate Gum Arabic Powder

Papaverine chlorohydrate

Ethoxazorutine ascorbic acid lacquer magnesium stearate gum arabic cum powder Glazed sugar

Gum arabic powder talc

Granulated sugar tartrazine carnauba wax

0.034 g 0.025 g 0.025 g 0.015 g 0.010 g 0.001 g

0.033 g '0.025 g 0.025 g 0.0075 g 0.006 g 0.0235 g.

0.033 g 0.025 g 0.025 g 0.00375 0.010 g 0.100 g 0.05325 g

Traces 0.050 g 0.270 g traces traces

Core 0.110 g

First coat

0.120 g

Second coating

0.250 g

Dragee layer

0.320 g

Total: 0.800 g

In dogs, whose metabolism is more active than that of humans, the presence of papaverine can be detected in the blood 30 minutes after taking such tablets, and the constancy of its content during

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more than six hours can then be increased again.

Example 2;
core

Active part of the beat O, (JO2'3 S. powdered sugar 0.029 S. Gum arabic powder 0.025 S. talc 0.006 S. Stearic acid 0.012 G Cetyl alcohol 0.002 Rubber lacquer (in the form of a 50% 0.0035 G Solution in 95% Aiko- get)

All ingredients are specified in the above Order combined and mixed, placed in a granulator, dried on sieves, and sieved on a No. 30 sieve.

The material is placed on the first rotating ring · BJnota 1/4 pressed. - 1 core for 0.08.

First serving

Active ingredient 0.0025 g

Powdered sugar 0.0335 g

Gum arabic powder 0.030 g

Talc 0.009 g

Stearic acid. 0.017 g

Cetyl alcohol 0.003 g

Rubber lacquer (in the form of a 50 # 0.005 g solution in 95 # alcohol)

All ingredients are combined and mixed in the specified order, placed in a granulator Sieve dried and sieved on a No. 30 sieve.

The material is on the second rotating ring Bicota 0 10/32 pressed. - 1 layer for 0.100 on core 0.08 - total 0.100.

2098U / 1613 BADORiGlNAL

Second serving

Active ingredient 0.0025 g

Powdered sugar 0.0765 g

Gfumiii arabicum powder 0.075 g

Talc 0.014 g

Stearic acid 0.022 g

Getyl alcohol 0.005 g

Rubber varnish (in ue of a 50 % ± 0.005 g solution in 95% alcohol

oaiiitli-ch «: components ν / earth in the specified Keihenfo.L ^ e added unit g-jiniecht, put in aine granulator, dried on sieves and placed on a No. 30 sieve. I) JIt; Material is shown on the third rotating ring Bi co ta 0 13/32 compressed - 1 layer for 0.800 on one of ü, U: 0 excessive li'ern - Lnsgtjsiunt Ü, 3ÖO.

Preparing for Dr agees:

On the 0.3BU g, finished i> your layer tablet te a coating up to a weight of 0.650 g is applied with a turbine.

Example 3 ι
core

Active component

talc

Glycerine stearate

110 mg

The glycerin stearate is in alcohol on top of the water bath dissolved, the mixture of active ingredient and talc with this solution is granulated, partly dried in ice, sifted, and drying is completed.

80 mg 10 mg 20th

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100 mg 20th mg 20th mg 20th mg

The material is placed on your first rotating ring "Hico ta pressed with stamps from 0 1/4.

First coat

Active component
Calcium carbonate
Lanolin'
Grummiarabi cum-powder he

95 consecutive alcohol and water ^{1β0 mg}

The active ingredient, calcium carbonate and gum arabic powder are mixed. The lanolin is dispersed in the hot alcohol, and the powder mixture ^r / ird moistened with this dispersion; the mixture is dried, pounded in a mortar, and water is added for the granulation.

The material is compressed on the second rotating ring Bicota with stamps from 0 3/8.

Second he coating

Active ingredient 120 mg

Kaolin 80 mg

Lanolin 30 mg

Arabine 30 mg

Alcohol and water ²⁷ ° ^mg

The procedure is the same as for the first layer. The pressing is done with stamps from 0 15/32 on the third rotating ring Bicota.

BATH 209814/1613

Example 4:

70 mg 20th mg 10 mg 15th mg mg

Active ingredient talc stearic acid gum lacquer ethyl phthalate

118 mg of 95 # alcohol

The stearic acid and the talc become in the heat mixed. The mixture is allowed to cool and finely pulverized. The active ingredient is added and mixed in; this is followed by granulation with the lacquer solution in alcohol and the atliyl phthalate, and also de granulation.

The material is compressed on the first rotating ring Bicota with stamps from 0 1/4.

First coat -

Active component

Icing sugar _- _w

Gum arabic powder 10 mg Jj

Stearic acid ^1ir * "~

Rubber lacquer atliyl phthalate

95 $ alcohol 127 mg

The manufacturing process is the same as for the core. The material is Bieota on the second rotating ring marked with stamps of 3/8.

80 mg 10 mg 10 mg 15th mg 10 mg 2 mg

BATH ORIGINAL 209-814 / 1613

Second coating

Active ingredient 100 mg

Icing sugar. 50 mg

Gum arabic powder 50 mg

Lacquer 5 mg

Stearic acid 20 mg

Talc 25 mg

250 mg "alcohol and water

The procedure is carried out in the same way as for the first coat. Rubber lacquer is added to the mixture and diluted alcohol are added, followed by drying and degranulation.

Example 5i

Active ingredient 70 mg

Levilit 10 mg

Talc 20 mg

Grated white wax 10 mg

Magnesium stearate 5 mg

95% alcohol ^{115 ing}

The active ingredient is mixed with the white wax in the heat, Levilit and talc is added and granulated with 95% alcohol; the magnesium stearate will admitted. The first Bioota rotating ring is pressed with stamps of 0 1/4.

First coat

Active component 80 mg BATH ORIGINAL Levilite 10 mg Icing sugar 20th mg Arabine powder 20th mg Grated white wax 12th ing Magnesium stearate 3 raft 95 # alcohol 145 mg 2098U / 1613

The procedure is done in the same way as for carried out the core. It will be on your second rotating ring ßicota mifc stamps from 0 3/3 compressible.

Second coating layer

Active ingredient 100 mg

Levilit 15 mg

G-glaze sugar 40 mg

Cfum arabic powder 80 mg

Grated it white awake 20 mg

Magnesium stearate .-, ■ 5 mg

.260 mg 95% alcohol

The procedure is the same as for that first bchiahb performed. It will be on the third rotating ring bico ba with stamps from 0 "15/32 pressed b.

2098U / 1613

Claims (4)

Claims; 1. Process for the production of multi-layer tablets with a concentrically arranged ivern urid one or several coating layers, characterized in that at least two of the same delaying constituents are incorporated, which differ due to the amount in which they are present and / or their nature that they differ according to the Incorporate different resolution times. 2. The method according to claim 1, characterized in that in the core and the layer (s) of the tablet, which are should dissolve delaying, one or more delaying components should be incorporated, whereby core and layer (s) may contain the same or different active ingredients. 3. The method according to claim 1-2, characterized in that the core and layer (s) pressed under different pressures will. 4. The method according to claim 1-3j, characterized in that that the core is produced under the strongest pressure and the subsequent layers under a lower pressure or under gradually decreasing pressures, especially when the retarding component is a resin how rubber lacquer is. For Les Laboratoires Dausse Lawyer 209814/1613