Method for production of coated tablets having cerebroprotective, antioxydant, and noothropic action

FIELD: medicine.

SUBSTANCE: claimed method includes blending of active base and auxiliary ingredients to form tablet corn, representing composition of sugar powder, monocrystalline cellulose, vinylpyrrolidone and calcium stearate; humidifying of obtained mixture; drying of obtained granules; dry granulation through granulator with standardized holes; pelletization of standardized granules to produce tablet corn; and coating. Mixture is humidified with 5-7 % starch mucilage in starch mucilage/humidifying mixture mass ratio of 1:25-30, wherein mixture is blending with starch mucilage for homogeneous distribution wet in whole mass.

EFFECT: tablets with increased hardness and enhanced pharmacological activity.

2 cl, 2 ex

 

The invention relates to medicine, in particular to pharmacotherapy, namely cerebroprotective, antioxidant, neuroprotective drugs with combined active base in coated tablets, and their manufacturing techniques.

Known nootropic drug tablets "piracetam", registration No. 95/174/6/82/624/24 from 29.09.95, (drugs of Ukraine, 1999-2000, 2, str-306).

Piracetam has a positive effect on metabolism, blood flow and bioenergetic processes.

The disadvantages of the known medicines are not has an antioxidant effect, slow pharmacological effect, manifested only in an hour, a limited range of pharmacological activity, the possibility of acute coronary insufficiency and the occurrence of dyspeptic symptoms.

In addition, the technology of manufacturing of tablets piracetam provided by mixing an active basis with auxiliary ingredients, moisturizing mixture, wet granulation, drying of granules, dry granulating calibrated granulator and pressing tablets-cores.

This increases costs and reduces the productivity of the manufacture of tablets.

Known cerebroprotective, antioxidant and nootropic drug in tab is edah coated on declarative patent of Ukraine # 55983 And, class a 61 K 31/40, a 61 K 31/41.

Known drug as an active Foundation contains a mixture of piracetam with thiotriazoline, as well as other ingredients to form the tablet core and shell powdered sugar, microcrystalline cellulose, polivinilpirolidon, oximeter cellulose, stearic acid or calcium stearate, and polyethylene oxide.

Pharmacological advantages of well-known medicinal product is due to vzaimopodderzhivayuschimi action thiotriazoline, which possesses antioxidant and cerebroprotective action, and piracetam, which owns nootropic action, along with metabolic regulatory mechanism of blood circulation contributes to the nervous mechanism of its regulation, increases the speed and force of impact of medicines on improvement of blood supply.

When this drug is not only preserves, but also expands the range of pharmacological effects, inherent thiotriazoline, and eliminates the aggravation of coronary insufficiency and dyspeptic phenomena, possible when using piracetam.

A disadvantage of the known means is, as in the above analogy, the need for surgery wet granulation in the manufacture of tablets.

A method of obtaining antiaggregative tools, improving the surrounding cerebral circulation, according to the patent of Russian Federation №2157209, class a 61 K 31/522.

The known method involves mixing the active base with auxiliary ingredients to form tablet cores, representing the composition of powdered sugar, microcrystalline cellulose, polyvinylpyrolidone; wetting the mixture with distilled water or starch paste when the mass ratio of the humidifier to irrigated mass 1:1,8-3,0; implementation of wet granulation, drying, dry granuliruta; the introduction of a salt of stearic acid and talc and the subsequent formation of granules into tablets-core; applying them to the shell.

This method is taken as a prototype of the proposed method to obtain drugs in the form of film coated tablets.

The disadvantages of this method are the wetlands of the mixture, excluding the arbitrary formation of various size granules in the process of moisture directly into the mixer, the increase in time duration of drying the wet granules; lack of firmness on the crushing ready tablets and a limited range of pharmacological actions.

The basis of the invention tasked to develop a method of manufacturing a coated tablets, providing technological advantages and improving the quality of the finished product in comparison with the analogues and the prototype.

The solution of this problem provides a method of manufacturing a coated tablets with cerebroprotective, antioxidant and neuroprotective effect, comprising mixing an active Foundation - piracetam and thiotriazoline and other ingredients to form the tablet core, which is the composition of powdered sugar, microcristalina cellulose, polyvinylpyrolidone and calcium stearate, moistening the mixture, drying, dry granuliruta calibrated through a pelleting, tableting granules into tablets-engine and transmission to the step of applying the membrane, and the moisture of the mixture to produce 5-7% starch paste at a mass ratio of paste to the humidified mixture of 1:25-30, stirring the mixture with a paste to the uniform distribution moisture throughout the mixture.

For the use of starch paste, with an initial moisture content of 1.8 to 2.2%.

In the solution for deposition of a coating on the tablet core using oxytropidoceras, titanium dioxide, tween-80, polivinilpirolidon and tartrazine.

Pharmacological and technological advantages of the method according to the invention:

a) reduction of production costs by combining the steps of wetting, wet granulation and reduce drying time;

b) stability;

in) strength (not less than 40 Newtons);

d) wynikamitest, namely, high solubility in water (more than 75% in 45 minutes);

d) the homogeneity of the mass.

The essence of the invention can be illustrated by the following examples of technological processes.

Example 1. Composition and production technology tablets-cores

The number of active substances and excipients, taken for the production of tablets-cores in kg:

Piracetam14,00
Thiotriazoline3,500
Sugar-powder1,840
Microcrystalline
cellulose (MCC-102)4,620
Polivinilpirolidon (PVP)0,245
Calcium stearate or acid
stearic0,228
Potato starch0,068

Refined sugar is ground in the mill. Piracetam, thiotriazoline, powdered sugar, calcium stearate, MCC and PVP is stirred for at least 3 minutes. The resulting mixture is humidified 6% starch paste (0.9 kg) and continue to mix for at least 5 minutes. The mass is dried at a temperature of 40°±2°With up to a residual moisture 2-3%. The dried granules are passed through a granulator to the diameter of the holes in the grid of 1.5-2 mm Table which aims to spend on a tablet machine RTM-41.

The average weight of the tablets is in the range of 0.333-0,368 g; solubility more than 75% in 45 minutes and strength of 40 Newton.

Example 2. The composition and coating technology tablets-cores

Ingredients for coating 25 kg of tablet cores shell:

Oksipropilmetiltselljulozy (OPMC-606)397,71 g
Titanium dioxidewith 46.6 g

Tween-8087,77 g
Polyvinylpyrolidone (PVP)150,86 g
Tartrazine2,74 g
Purified water11,8 kg

Preparation system for coating tablets-cores: 397,71 g OPMC-606 fill of 5 kg of boiling purified water, 3-4 hours after complete swelling OPMC the mixture was diluted with 2.8 kg of purified cold water. In parallel, prepare a solution of PVP 150,86 g PVP and 3 kg of purified water when heated. Pound in a mortar 46,6g titanium dioxide with 87,77 g of tween-80 and wash 0.7 kg purified water, 2,74 g tartrazine dissolved in 0.3 kg purified water. Prepared solutions OPMC, PVP and tartrazine mix, add a mixture of titanium dioxide with a twin-80, which wash 0.7 kg of purified water. The resulting mixture was filtered through gauze.

Coating of tablets is carried out in the apparatus pseudotype the layer at a temperature of 90-95° (Coverage). The feed rate of film-forming mixture of 400 ml per minute. After the filing of the whole mixture for coating tablets is maintained at the same temperature for drying.

The finished tablets unload and after cooling packaged. The obtained tablets are yellow in color.

Average weight is within 0,338-0,374, the solubility of not less than 75% in 45 minutes and strength of 40 Newton.

1. A method of manufacturing a coated tablets with cerebroprotective, antioxidant and neuroprotective effect, comprising mixing an active Foundation - piracetam and thiotriazoline and auxiliary ingredients to form the tablet core, which is the composition of powdered sugar, microcrystalline cellulose, polyvinylpyrolidone and calcium stearate, moistening the mixture, drying, dry granuliruta calibrated through a pelleting, tableting granules into tablets-engine and transmission to the step of applying the membrane, and the moisture of the mixture to produce 5-7% starch paste at a mass ratio of paste to the humidified mixture of 1:25-30, stirring the mixture with a paste to the uniform distribution of moisture throughout the mixture.

2. The method according to claim 1, characterized in that for the preparation of paste used potato starch with an initial moisture content of 1.8 to 2.2%.

3. The method according to claims 1 and 2, characterized in that when s is gotowka solution for deposition of a coating on the tablet core oksipropilmetiltselljuloza pour boiling water in the ratio 1:12-13, maintain 3-4 h until complete swelling oksipropilmetiltselljulozy, diluted with cold water in the ratio of dry mass oksipropilmetiltselljulozy to cold water 1:7-8, fray carefully tween-80 and titanium dioxide in a ratio of 1:1,8-2, transfer the mixture into a solution of oksipropilmetiltselljulozy, separately poured cold water polivinilpirolidon in the ratio of 1:19-20, heated to complete dissolution of polyvinylpyrolidone, cooled, poured into a solution of oksipropilmetiltselljulozy, dissolve tartrazine in warm water at a ratio of 1:109-110, making the solution in the solution oksipropilmetiltselljulozy, carefully mix the resulting solution is filtered through two layers of cheesecloth and transfer to the stage applying a coating on the tablet core.



 

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