RU2275910C2 - Method for production of coated tablets having cerebroprotective, antioxydant, and noothropic action - Google Patents

Abstract

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

Description

The invention relates to medicine, in particular to pharmacotherapy, namely to cerebroprotective, antioxidant, nootropic drugs with a combined active base in coated tablets, and the technology for their manufacture.

Known nootropic drug in tablets "piracetam", registration number 95/174/6/82/624/24 from 09/29/95 (Medicines of Ukraine, 1999-2000, 2 volume, pp. 303-306).

Piracetam has a positive effect on metabolic processes, blood supply and bioenergy processes.

The disadvantages of the known drugs are antioxidant, delayed pharmacological action, manifested only after an hour, a limited spectrum of pharmacological activity, the possibility of exacerbation of coronary insufficiency and the occurrence of dyspeptic phenomena.

In addition, the technology for the manufacture of piracetam tablets provides for mixing the active base with auxiliary ingredients, moistening the mixture, wet granulation, drying granules, dry granulation with a calibrated granulator and pressing tablet cores.

This increases costs and reduces tablet manufacturing productivity.

Known cerebroprotective, antioxidant and nootropic drug in coated tablets according to the declaration patent of Ukraine No. 55983 A, class. A 61 K 31/40, A 61 K 31/41.

The known drug as an active base contains a mixture of piracetam with thiotriazolin, and as an auxiliary ingredient for the formation of the tablet core and shell, powdered sugar, microcrystalline cellulose, polyvinylpyrrolidone, hydroxymethyl cellulose, stearic acid or calcium stearate, polyethylene oxide.

The pharmacological advantages of the known drug are due to the mutually potentious effect of thiotriazolin, which has an antioxidant and cerebroprotective effect, and piracetam, which has a nootropic effect, which, along with the metabolic mechanism of blood supply regulation, contributes to the emergence of a nervous mechanism for its regulation, increases the speed and strength of the drug's effect on improving blood supply.

At the same time, the drug not only preserves, but also expands the spectrum of pharmacological action inherent in thiotriazoline, and eliminates exacerbation of coronary insufficiency and dyspeptic phenomena possible with piracetam.

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

A known method of producing an antiplatelet agent that improves cerebral circulation, according to the patent of the Russian Federation No. 2157209, class. A 61 K 31/522.

The known method includes mixing the active base with auxiliary ingredients to form a tablet core representing the composition of powdered sugar, microcrystalline cellulose, polyvinylpyrrolidone; moistening the mixture with distilled water or starch paste with a mass ratio of humidifier to the moistened mass of 1: 1.8-3.0; the implementation of wet granulation; drying; dry granulation; the introduction of a salt of stearic acid and talc and the subsequent formation of granules in the tablet core; coating them.

This method is taken as a prototype of the proposed method for producing a medicinal product in the form of coated tablets.

The disadvantages of this method are waterlogging of the mixture, eliminating the arbitrary formation of granules of different sizes in the process of wetting directly in the mixer, an increase in the duration of the drying of wet granules; insufficient hardness to crush finished tablets and a limited spectrum of pharmacological action.

The basis of the invention is the task to develop a method for the manufacture of coated tablets, providing technological advantages and improving the quality of finished products in comparison with the above analogues and prototype.

The solution of this problem provides a method for the manufacture of coated tablets with cerebroprotective, antioxidant and nootropic effects, including mixing the active base - piracetam and thiotriazoline and auxiliary ingredients for the formation of a tablet core, which is a composition of powdered sugar, microcrystalline cellulose, polyvinylpyrrolidone and calcium stearate the resulting mixture, drying, dry granulation through a calibrated granulator, pelletizing tablets into tablets pa and the transfer to shell deposition step, wherein the moisturizing mixture produced 5-7% starch paste at a weight ratio of paste to the humidified mixture 1: 25-30, stirring the mixture with a paste to a uniform moisture distribution throughout the mixture.

At the same time, starch with an initial moisture content of 1.8-2.2% is used for the paste.

In the solution for coating the core tablets, hydroxypropylmethylcellulose, titanium dioxide, tween-80, polyvinylpyrrolidone and tartrazine are used.

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

a) reducing production costs by combining the stages of wetting, wet granulation and reducing drying time;

b) stability;

c) strength (not less than 40 Newtons);

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

e) mass uniformity.

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

Example 1. The composition and production technology of tablet cores

The number of active and excipients taken for the production of tablet cores in kg:

Piracetam 14.00 Thiotriazoline 3,500 Powdered sugar 1,840 Microcrystalline cellulose (MCC-102) 4,620 Polyvinylpyrrolidone (PVP) 0.245 Calcium Stearate or Acid stearic 0.228 Potato starch 0,068

Refined sugar is ground in a mill. Piracetam, thiotriazolin, powdered sugar, calcium stearate, MCC and PVP are mixed for at least 3 minutes. The resulting mixture was moistened with 6% starch paste (0.9 kg) and continued to mix for at least 5 minutes. The mass is dried at a temperature of 40 ° C ± 2 ° C to a residual moisture content of 2-3%. The dried granules are passed through a granulator with a hole diameter of 1.5-2 mm on a grid. Tableting is carried out on a RTM-41 tablet machine.

The average weight of the tablets is in the range of 0.333-0.368 g; solubility of more than 75% in 45 minutes and strength of 40 newton.

Example 2. Composition and coating technology of tablet cores

The composition of the ingredients for coating 25 kg of tablet cores with a shell:

Oxypropyl methylcellulose (OPMC-606) 397.71 g Titanium dioxide 46.6 g

Tween 80 87.77 g Polyvinylpyrrolidone (PVP) 150.86 g Tartrazine 2.74 g Purified water 11.8 kg

Preparation of a system for coating tablet cores: 397.71 g of OPMTs-606 are poured into 5 kg of boiling purified water, 3-4 hours after complete swelling of the OPMTs, the mixture is diluted with 2.8 kg of purified cold water. In parallel, a PVP solution is prepared from 150.86 g of PVP and 3 kg of purified water when heated. Rub 46.6 g of titanium dioxide with 87.77 g of Tween-80 in a mortar and wash off 0.7 kg of purified water, 2.74 g of tartrazine are dissolved in 0.3 kg of purified water. The prepared solutions of HMPC, PVP and tartrazine are mixed, a mixture of titanium dioxide and tween-80 is added, which is washed off with 0.7 kg of purified water. The resulting mixture was filtered through cheesecloth.

Coating of the tablets is carried out in a pseudo-boiling layer apparatus at a temperature of 90-95 ° C (in the coating zone). The feed rate of the film-forming mixture is 400 ml per minute. After supplying the entire coating mixture, the tablets are held at the same temperature for drying.

Ready tablets are unloaded and packaged after cooling. The resulting tablets are yellow.

The average weight is within 0.338-0.374 g. Solubility is not less than 75% in 45 minutes and strength is 40 Newton.

Claims (3)

1. A method of manufacturing a coated tablet with a cerebroprotective, antioxidant and nootropic effect, comprising mixing the active base - piracetam and thiotriazoline and auxiliary ingredients for forming a tablet core, which is a composition of powdered sugar, microcrystalline cellulose, polyvinylpyrrolidone and calcium stearate, moistening the mixture obtained drying, dry granulation through a calibrated granulator, pelletizing pellets into tablet cores and transferring to the coating application step hi, and the mixture is moistened with 5-7% starch paste with a mass ratio of paste to moistened mixture of 1: 25-30, mixing the mixture with paste until the moisture is evenly distributed throughout the mixture. 2. The method according to claim 1, characterized in that for the preparation of the paste using potato starch with an initial moisture content of 1.8-2.2%. 3. The method according to claims 1 and 2, characterized in that when preparing the solution for coating the tablet cores, the hydroxypropyl methylcellulose is poured with boiling water in a ratio of 1: 12-13, it is held for 3-4 hours until the hydroxypropyl methylcellulose is completely swollen, diluted with cold water in the dry weight ratio of hydroxypropyl methylcellulose to cold water is 1: 7-8, tween-80 and titanium dioxide are carefully rubbed in a ratio of 1: 1.8-2, the mixture is transferred to a solution of hydroxypropyl methylcellulose, polyvinylpyrrolidone is individually poured with cold water in a ratio of 1: 19-20, heated to the floor solution of polyvinylpyrrolidone, cooled, poured into a solution of hydroxypropyl methylcellulose, dissolve tartrazine in warm water at a ratio of 1: 109-110, adding the solution to a solution of hydroxypropyl methylcellulose, thoroughly mix the resulting solution, filter through two layers of gauze and transfer to the stage of coating on the tablet core .