Method of producing tablets

专利摘要:

公开号:SU1356951A3
申请号:SU843725952
申请日:1984-04-16
公开日:1987-11-30
发明作者:Циренберг Бернд；Раярам Гупте Арун
申请人:Берингер Ингельгейм Кг (Фирма)；
IPC主号:

专利说明:

one
The invention relates to pharmacology, and in particular to methods for preparing tablets.
The aim of the invention is to extend the release of the substance.
The goal is achieved by using mainly konidin as the active substance, and as a copolymer — acrylic and / or methacrylic acid and / or their acrylic esters with a grain size of 50–500 nm and after evaporation of the solvent temperature below the glass transition temperature.
Example 1. In the tank serves 40 g of the obtained emulsion polymerization of a copolymer of complex
acrylic acid methyl and ethyl esters and methacrylic acid methyl and ethyl esters in a 50:50 molecular ratio, having a grain size of 50n 5 g of clonidine (-2- (2,6-dichloromethyl-imino) -imidazolidine) as base and 455 g of acetone and mix until a completely clear solution is obtained. The resulting solution is transferred to a bowl, from which the solvent 1110 can be evaporated at room temperature. The remaining film containing the active substance is cooled to a temperature with dry ice and, together with lactose, is crushed in portions while cooling in a mill with rotating knives. The solid and lactose are taken in a weight ratio of 9: 1. A free flowing powder is obtained, which is an active substance containing an acrylate polymer with a grain size of 10-500 µm.
The resulting mixture, which is an acrylate polymer grain, containing the specified active substance in a molecular dispersed form and milk sugar, together with milk sugar and polyvinylpyrrolidone, is granulated using; water, followed by pressing. In Tc1 cells weighing 180.0 mg with the addition of auxiliary substances of corn starch, colloidal silicon e.E1O acid and magnesium stearate on an eccentric press, equipped with a device for performing overs.

The composition of the tablet, mg Acrylate polymer as a carrier
Milk sugar
Polyvinyl pyrrolidone Corn starch Colloidal silicic acid Magnesium stearate
2.50 158.75 3.75 13.50
1,00 2л50
180.00
Acrylate polymer has the following composition, mg / 2.50 mg of carrier:

0.25 2.00 0.25
Tensile strength 2.16 n / mm, decay 61 Co
The isolation of the active substance in the test tube is determined at 37 ° C in the apparatus according to the American standard, and 4 tablets are tested for each container. The transition from the gastric juice to the intestinal takes place after 1 hour, and the analytical determination of the active substance is carried out by liquid chromatography under pressure. After the disintegration of the tablet, in addition to water-insoluble auxiliaries, the acrylate polymer grains remain active, from which the active substance clonidine diffuses in the form of a base.
Data on the release of the active substance is as follows:
Time, h - Amount of released clonidine,%
0,2529,1
J39,5
2 4 6
54.9 60.8 68.3
31
Example 2. 50 g of a copolymer obtained by emulsion polymerization of a copolymer of methyl and ethyl esters of acrylic acid and methyl and ethyl esters of methacrylic acid in a molar ratio of 50:50, having a grain size of 150 nm, 2.33, are fed into the container. g of clonidine as a base and 5.82 g of polyvinylpyrrolide
on, mix with 1000 ml of acetone and dissolve with stirring. After dissolving the solvent is evaporated in an open bowl, the resulting film is crushed and processed into tablets as in Example 1.
The determination of the release of the active substance is carried out analogously to example 1.
Data on the release of the active substance:
Time h
The number of released clonidine,%
12.6 24.7 33.3 44.2 52.5
Approx. 40 g of the resulting emulsion polymerization of a copolymer of methyl and ethyl acrylic acids and methyl and ethyl esters of methacrylic acid in a 50:50 molecular ratio, 50n grains, 5 g clonidine (-2- ( 2,6-dichloromethylimino) imidazolidine} as a base and 455 g of acetone and mix until a completely clear solution is obtained. The resulting solution is transferred to a bowl from which the solvent can be evaporated at room temperature. The substance of the film is cooled to a temperature of -40 ° C with dry ice and, together with lactose, is crushed in portions when cooled in a mill with rotates with knives. At the same time, the solid and lactose are taken in a weight ratio of 9: 1.
a non-flowing powder, which is an active substance containing an acrylic polymer with a grain size of 10-500 µm. The resulting mixture together with the required amount of milk sugar and polyvinylpyrrolidone is granulated using water, followed by pressing into tablets weighing 180.0 mg with the addition of auxiliary substances (corn starch, colloidal silicic acid and magnesium stearate) with an eccentric press equipped with a notch tool
The composition of the tablet, mg:
Acrylate
0
five
0
polymer as carrier Milk sugar
Polyvinyl Feast Roll Corn Starch Colloidal Silicic Acid Magnesium Stearate
2.50 158.75 3.75 13.50
1.00 0.50
40
180.00
The composition of the acrylate polymer is as follows, mg / 2.50 mg of carrier: Clonidine as base .0.25 Acrylate
polymer2,00
Lactic
sugar0.25
Tensile strength 2.16 n / mm, decay 61, p.
The selection of the active substance in the tube is determined at 37 ° C. The results of the active substance are as follows:
Time, 4f Amount
yielded clonidine,%
0,251,7
13.3
45
50
2 4 6
A, 7 6.6 8.1
513569516
We obtain the proposed 1m way that, with the aim of
 the tablet has a longer period of prolongation of the release of the substance, release of the active substance, i.e. it is used up to 6 hours as the active substance, clonidine is used mainly, acrylic and / or

权利要求:
Claims (1)
[1]
The invention claims methacrylic acid and / or their acrylic esters with a grain size of 50. A method for preparing tablets by 500 nm and, after evaporation of the displaced active substance with the coagulum, is ground in the presence of an inertilimeter with an organic solvent.
and evaporation of the solvent, tl and glass transition temperature.

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

---

DE19833314003|DE3314003A1|1983-04-18|1983-04-18|DIVISIBLE TABLET WITH DELAYED ACTIVE SUBSTANCE RELEASE AND METHOD FOR THE PRODUCTION THEREOF|

---