RU2448686C1 - Solid individual high 2-ethyl-6-methyl-3-pyridin-3-ole hydrochloride dosage form and method for preparing it - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to chemical-pharmaceutical industry, and concerns a solid individual dosage forms exhibiting antistress, moderate tranquilising, nootropic, antiamnestic and antihypoxic action, containing as an active ingredient, an effective amount of 2-ethyl-6-methyl-3-pyridin-3-ole hydrochloride and pharmaceutically acceptable excipients, which contains 65.0-92.5 wt % of 2-ethyl-6-methyl-pyridin-3-ole hydrochloride, 25.6-2.5 wt % twice-substituted calcium phosphate as an excipient, 0.4-1.9 wt % of oxypropylcellulose as a binding agent and 9.0-0.6 wt % of flowing and anti-adhesion substances. Said dosage form may be presented in the form of a optionally coated marked tablet.

EFFECT: invention provides a method for making said solid individual dosage form, has high bioavailability and shelf life to 5 years.

3 cl, 9 ex, 7 tbl

Description

FIELD OF THE INVENTION

The present invention relates to the field of pharmacology. More specifically, the invention relates to the production of solid dosage forms with a high content of 2-ethyl-6-methyl-3-pyridin-3-ol hydrochloride (methylethylpyridinol hydrochloride), which are highly bioavailable and have a long shelf life.

State of the art

Medicines containing methyl ethyl pyridinol in the form of pharmaceutically acceptable salts have a pronounced antistress, moderate tranquilizing, nootropic, antiamnestic and antihypoxic effect. As a result, they are used, for example, in the treatment of mild cognitive impairment, anxiety and other neurotic conditions, neurocirculatory dystonia, and also in narcology to improve the condition of patients suffering from alcohol or drug addiction, both in acute intoxication and at the stage of withdrawal.

Known dosage forms include sterile injectable solutions and solid preparations. For intravenous and intramuscular administration, a 5% solution of methylethylpyridinol succinate (trademarks: mexidol, mexiprim, mexifine) in water for injection is used, optionally containing sodium metabisulfite as an antioxidant. The drug is placed in ampoules of 2 or 5 ml. For oral administration, coated tablets or hard capsules containing 100-125 mg of methylethylpyridinol succinate and pharmaceutically acceptable excipients are used.

In the patent of the Russian Federation 2065299 (publ. 08.20.1996), coated tablets are disclosed containing 16.7-41.6 wt.% Mexidol, 16.7-33.3 wt.% White clay, the same amount of potato starch, according to 0.3-0.5 wt.% Calcium stearate, stearic acid and methyl cellulose, as well as 0.5-1.0 wt.% Talc. The tablet is coated, containing (as a percentage of the shell weight) 25.0-50.0% methyl cellulose and 8.3-25% tween-80 and titanium dioxide. Despite the significant total content of starch and white clay (33-67 wt.%) In the composition of the tablet core, it is not possible to achieve stable tablet quality, and, starting from the manufacturing stage, the core turns yellow.

In the patent of the Russian Federation 2144822 (publ. 27.01.2000) describes the composition of the mass for filling gelatin capsules (0.1 g of active ingredient per capsule) containing 50 wt.% Mexidol, 40.5-50.5 wt.% Potato starch, 2.4-2.8 wt.% Polyvinylpyrrolidone, 0.9-1.1 wt.% Magnesium stearate, 0.9-1.1 wt.% Talc.

In the patent of the Russian Federation 2145855 (publ. 27.02.2000) disclosed the composition of another mass to fill similar capsules. The mass contains 30-60 wt.% Mexidol, 17.0-35 wt.% Potato starch, 2.5-3.5 wt.% Polyvinylpyrrolidone, 0.8-1.2 wt.% Magnesium stearate, 7.7- 12.2 wt.% Microcrystalline cellulose, 12.0-18.0 wt.% Milk sugar. The main disadvantage of the proposed compositions is the decrease in their quality during storage. In addition, the high sugar content of milk and starch (from 29% to 53 wt.% In total) creates the prerequisites for the contamination of the stored preparation with microorganisms and their metabolic products.

In patent 2205640 (publ. 10.06.2003) pharmaceutical compositions are described which are a solution for injection, granular powder for encapsulation and a composition for tabletting, characterized in that they additionally contain 0.5-5.0 wt.% Succinic acid. The patent specification states that succinic acid is used as a stabilizer and also increases the content of reduced glutathione, i.e. has an additional biological effect.

The granular powder for encapsulation disclosed in said patent contains 50.0-60.0 wt.% Mexidol, 0.5-5.0 wt.% Succinic acid, 0.0-0.2 wt.% Trilon B, 25.0 -35.0 wt.% Microcrystalline cellulose, 15.0-20.0 wt.% Starch, 4.0-6.0 wt.% Low molecular weight polyvinylpyrrolidone, 0.9-1.3 wt.% Magnesium stearate and 0, 8-1.1 wt.% Talc. The pharmaceutical composition intended for tabletting contains 50.0-60.0 wt.% Mexidol, 0.5-5.0 wt.% Succinic acid, 0.0-0.2 wt.% Trilon B, 14.0- 25.0 wt.% Microcrystalline cellulose, 15.0-25.0 wt.% Starch, 4.0-6.0 wt.% Low molecular weight polyvinylpyrrolidone, 0.0-5.0 wt.% Sodium starch glycolate, 0, 8-1.0 wt.% Magnesium stearate, 0.0-1.0 wt.% Talc and 0.0-3.0 wt.% Collidone CL. The proposed compositions are stable for 2 years.

The main disadvantage of all known solid dosage forms is the low content of the active component (not more than 60 wt.%). In particular, the consequence of this is an increase in the weight and size of the tablet or capsule containing a therapeutically effective amount of the active component. This can be difficult to administer, especially to patients suffering from neurotic disorders. In addition, the need for the introduction of significant quantities of excipients and the application of protective shells of complex composition to ensure a long shelf life increases the cost of production of the finished product due to an increase in the share of costs for materials and processing equipment.

Thus, there is a need to create preparations with a high content of methyl ethyl pyridinol having a long shelf life.

Description of the invention

The aim of the present invention is to provide solid dosage forms with a high content of methyl ethyl pyridinol hydrochloride having a long shelf life and satisfying all the requirements of the State Pharmacopoeia of the Russian Federation.

The authors of the present invention conducted extensive studies to overcome the disadvantages of the prior art and created solid individual dosage forms that meet all the requirements of the State Pharmacopoeia of the Russian Federation, containing a significantly smaller number of components in smaller quantities with respect to methylethylpyridinol hydrochloride as an active component.

In accordance with a first embodiment of the present invention, there is provided a solid, individual dosage form with a high content of methylethylpyridinol hydrochloride having a pronounced antistress, moderate tranquilizing, nootropic, antiamnestic and antihypoxic effect, comprising as an active component an effective amount of 2-ethyl-6-methyl-3-pyridine -3-ol hydrochloride and pharmaceutically acceptable excipients containing 65.0-92.5 wt.% 2-ethyl-6-methyl-3-pyridin-3-ol hydrochloride, 25.6-2.5 m pp.% filler, 0,4-1,9 wt.% binder and 9,0-0,6 wt.% of substances providing fluidity and prevent sticking.

In a preferred embodiment of the dosage form, excipients are selected from the group consisting of lactose, calcium phosphate disubstituted, microcrystalline cellulose, binders are selected from the group consisting of starch, polyvinylpyrrolidone, hydroxypropylcellulose, and substances that provide fluidity and prevent adhesion are selected from the group consisting of calcium stearate, magnesium stearate, aerosil.

The term "solid individual dosage form" refers to a physically discrete portion of a pharmaceutical composition containing a certain amount of active ingredient.

The term “capsule” has a generally accepted meaning in the art and preferably refers to hard capsules, more preferably hard gelatin capsules.

In a first preferred embodiment of the hard gelatin capsule, the binder is hydroxypropyl cellulose and aerosil is a fluidity and anti-sticking agent.

In a second preferred embodiment of the hard gelatin capsule, the binder is polyvinylpyrrolidone or starch paste, and aerosil is a fluidity and anti-sticking agent.

The term “tablet” has a generally accepted meaning in the art and preferably refers to flat cylindrical tablets with a risk, more preferably additionally coated.

In a preferred embodiment, the tablet with a risk is selected from the group consisting of lactose and calcium phosphate disubstituted, the binder is selected from the group consisting of hydroxypropyl cellulose and polyvinylpyrrolidone, and the substance providing fluidity and preventing adhesion is magnesium stearate.

In an even more preferred embodiment, the tablet is coated with an Opadry polyvinyl acetate shell, the shell weight being not more than 2.5% by weight of the dosage form.

These solid dosage forms can be prepared by conventional methods, for example by wet granulation, using excipients known to a person skilled in the art: fillers, binders, flow agents, strength, anti-stick agents, coating formulations, etc.

As fillers, for example, lactose, calcium phosphate disubstituted, microcrystalline cellulose can be used. Binders can be various types of starch, polyvinylpyrrolidone, hydroxypropyl cellulose. To ensure fluidity and prevent adhesion, calcium stearate, magnesium stearate, aerosil can be introduced into the composition.

To protect the active component from oxidation induced by the action of heat, light and moisture, it can be introduced into hard capsules, for example gelatin capsules. Alternatively, a solid dosage form in accordance with the present invention may be presented in the form of coated tablets. When choosing a coating composition, the specialist should be guided by the technological parameters of the coating process, protective properties, as well as the requirements for the finished dosage form.

In particular, aqueous coating compositions based on polyvinyl alcohol, polyvinyl acetate and polyvinyl acetate phthalate can be used. Examples of polyvinyl alcohol-based coating compositions include, without limitation, product groups manufactured by DuPont (trademark Elvanol) and Sekisui Specialty Chemicals (trademark Celvol). Polyvinyl acetate and polyvinyl acetate phthalate coating compositions include, but are not limited to, products sold by BSPI Holdings LLC (Opadry trademark). Choosing the right product is the responsibility of the average person skilled in the art. In particular, Opadry and Opadry II coating compositions are preferred, and in order to provide greater protection against atmospheric moisture without compromising disintegration under the conditions of administration, the most preferred Opadry amb composition based on polyvinyl acetate phthalate.

In accordance with a second embodiment of the present invention, there is provided a method for preparing a solid, individual dosage form for which:

1) prepare purified water to perform all technological and auxiliary operations that meets all the requirements of current regulatory documents,

2) prepare a humidifier solution containing 5-10 wt.% A binder that increases the adhesion between the particles of the components of the mixture to fill capsules or tablets,

3) separate sifting of methyl ethyl pyridinol hydrochloride and, if necessary, auxiliary substances, such as fillers, through sieves with openings of 0.10-0.25 mm,

4) sifted methylethylpyridinol hydrochloride and fillers are mixed until a homogeneous mass is obtained,

5) moisten the resulting mass with a humidifier solution until the moisture distribution is even,

6) the moistened mass is granulated,

7) the wet granules are dried at a temperature of 40-50 ° C until a residual moisture content of 1.5-4.0% is reached,

8) the dried granules are subjected to dry granulation and dusting with a substance that improves the fluidity of the granules and reduces their adhesion,

9) the obtained granules are pressed into tablets, which are then de-dusted and optionally coated with a tablet core temperature of 30 to 50 ° C, an inlet temperature of the device from 50 to 80 ° C and a relative humidity of less than 50%, or

capsules, preferably hard gelatine capsules, are filled with the obtained granules, and

10) ready-made individual dosage forms are packaged and marked on the packaging to identify the drug and apply instructions for use.

The choice of equipment for performing these operations is within the competence of the average person skilled in the art, who must take into account the restrictions imposed by the properties of methylethylpyridinol hydrochloride and excipients on the process parameters.

In particular, purified water must meet all the requirements of regulatory documents in force in this field. Water of this quality is prepared, for example, in an aquadistillator. Sieve for sifting is chosen based on the features of the device for granulating, tabletting or filling capsules. It is desirable that the size of the sieve openings be 0.10-0.25 mm. For drying, for example, drying ovens are used, in the whole volume of which the temperature of 40-50 ° C is uniformly maintained. Tableting is carried out using well-known standard devices, such as, for example, tablet machines with interchangeable punches and dies.

The application of coating compositions in the form of an aqueous suspension is preferably carried out at a temperature of tablet cores from 30 to 50 ° C, a temperature at the inlet of the apparatus from 50 to 80 ° C and a relative humidity of less than 50%. To ensure the preservation of the properties of methyl ethyl pyridinol hydrochloride at the production stage and to provide the required stability of the finished dosage form in the form of a film-coated tablet, a residual moisture content of not more than 4%, preferably not more than 3%, should be provided.

The following examples illustrate particular preferred embodiments of the present invention.

Example 1. Hard gelatin capsules

To carry out all the technological and auxiliary operations, purified water is prepared in an akvadistillyator, which meets all the requirements of regulatory documents in force in this field. By mixing until 5.0 g of polyvinylpyrrolidone with 45 ml of purified water is completely dissolved, a 10% solution of polyvinylpyrrolidone is prepared, used as a humectant to increase the adhesion between the particles of the components of the tabletting mixture.

Separate screening of methyl ethyl pyridinol hydrochloride, a filler based on corn starch and pregelatinized starch (trademark StarCap 1500, registered by BPSI Holdings, LLC) and microcrystalline cellulose through sieves with a hole size of 0.15 mm. Sifted methylethylpyridinol hydrochloride (0.153 kg), microcrystalline cellulose (0.003 kg) and StarCap 1500 filler (0.003 kg) are mixed in a ball mill for 30 minutes.

Next, wet granulation and drying are performed, for which, first, in the same ball mill, a 10% solution of polyvinylpyrrolidone (3 × 10 ml) is added to the dry mixture until the moisture is evenly distributed. The moistened mass is granulated by passing through a granulator with a hole size of 1.0 mm. Wet granules are dried in an oven at a temperature of 40 ° C until a residual moisture content of 2.0-3.5% is reached.

The dried granules are then subjected to dry granulation and dusting. For this, the dried granules are passed through a granulator with a hole size of 1.0 mm. To improve the fluidity of the granules and reduce adhesion, magnesium stearate is added to the granulate in an amount of 1,558 g (1% of the total mass). Dusting is carried out for 10 minutes

Then, in the encapsulation apparatus, open hard gelatin capsules (size No. 1) are filled with the resulting mass, and then the capsules are closed. Ready-made filled capsules are packed in blisters (10 or 20 pieces each) or in polymer jars with a screw neck and a screw-on lid for medicines and vitamins (30 or 50 pieces each). The packaging is labeled to identify the drug and directions for use are applied.

Disintegration: 5-7 minutes.

Table 1 shows the absolute and relative composition of the contents of the capsule.

Table 1 Name of components Content in one capsule g % Methylethylpyridinol hydrochloride 0.250 92.6 Microcrystalline cellulose 0.007 2.6 Starch-based filler (StarCap 1500) 0.005 1.9 Polyvinylpyrrolidone 0.005 1.9 Magnesium stearate 0.003 1,0 The mass of the contents of the capsule 0.270 100.0

Example 2. Hard gelatin capsules

The capsule preparation procedure described in Example 1 is repeated using a smaller ball mill or a mortar and pestle for mixing. Pre-sieved powders of methylethylpyridinol hydrochloride (2.5 g) and microcrystalline cellulose (1.1 g) are thoroughly homogenized. The resulting mixture is moistened with the required volume of a 5.0% aqueous hydroxypropyl cellulose solution, granulated and dried to a residual moisture content of 1.5-2.5%. The dried granules are ground in a granulator, after which 0.31 g of aerosil is dusted. The obtained granulate is placed in hard gelatin capsules at the rate of 0.250 g of Mexidol per capsule.

Disintegration: 5-7 minutes.

Table 2 shows the absolute and relative composition of the contents of the capsule.

table 2 Name of components Content in one capsule g % Methylethylpyridinol hydrochloride 0.250 63,4 Microcrystalline cellulose 0,110 27.9 Hydroxypropyl cellulose 0.003 0.8 Aerosil 0,031 7.9 The mass of the contents of the capsule 0.394 100.0

Example 3. Hard gelatin capsules

The capsule preparation procedure described in Example 2 is repeated using a 5.0% aqueous solution of polyvinylpyrrolidone as a binder. Disintegration: 6-8 minutes.

One capsule contains 0.250 g (63.4 wt.%) Of methylethylpyridinol hydrochloride.

Example 4. Hard gelatin capsules

The capsule preparation procedure described in Example 2 is repeated using 5.0% starch paste as a binder, and 0.36 g of calcium stearate is used for dusting. Disintegration: 5-8 minutes.

Table 3 shows the absolute and relative composition of the contents of the capsule.

Table 3 Name of components Content in one capsule g % Methylethylpyridinol hydrochloride 0.250 62.5 Microcrystalline cellulose 0,110 27.5 Starch paste 0.004 1,0 Calcium stearate 0,036 9.0 The mass of the contents of the capsule 0.400 100.0

Example 5. Tablets

To carry out all the technological and auxiliary operations, purified water is prepared in an akvadistillyator, which meets all the requirements of regulatory documents in force in this field. By mixing until 5.0 g of polyvinylpyrrolidone with 90 ml of purified water is completely dissolved, a 5% hydroxypropyl cellulose solution is prepared, which is used as a humidifier to increase the adhesion between the particles of the components of the tabletting mixture.

Separate screening of methylethylpyridinol hydrochloride and lactose as a filler is carried out through sieves with a mesh size of 0.15 mm. The sieved methylethylpyridinol hydrochloride (25.0 g) and lactose (10.0 g) are mixed in a ball mill for 30 minutes. The resulting mass in the same mill is moistened with 5% of the required volume of a 5.0% aqueous hydroxypropyl cellulose solution until the moisture is evenly distributed. The moistened mass is granulated by passing through a granulator with a hole size of 1.0 mm.

Wet granules are dried in an oven at a temperature of 45 ° C until a residual moisture content of 1.5-2.5% is reached. The dried granules are then subjected to dry granulation, for which they are passed through a granulator with a hole size of 1.0 mm, and then powdered with magnesium stearate (0.35 g) for 10 minutes to improve the fluidity of the granules and reduce their adhesion.

The granules obtained are pressed into 0.350 g tablets in a Korsch tablet press equipped with spherical punches. Dust-free tablets on a metal sieve with a hole size of 3-4 mm. Get tablets weighing 0.350 g, containing 0.250 g of methylethylpyridinol hydrochloride.

Disintegration: 5-7 minutes.

Table 4 shows the absolute and relative composition of the tablet.

Table 4 Name of components Content in one capsule g % Methylethylpyridinol hydrochloride 0.250 64.1 Lactose 0,100 25.6 Hydroxypropyl cellulose 0.005 0.4 Magnesium stearate 0,035 8.9 Tablet weight 0.390 100.0

Example 6. Tablets

The tablet preparation procedure described in Example 5 is repeated using disubstituted calcium phosphate as a filler, and a 5.0% solution of polyvinylpyrrolidone is used as a binder.

Disintegration: 6-8 minutes.

One tablet contains 0.250 g (64.1 wt.%) Of methylethylpyridinol hydrochloride.

Example 7. Coated Tablets

To carry out all the technological and auxiliary operations, purified water is prepared in an akvadistillyator, which meets all the requirements of regulatory documents in force in this field. By mixing until 5.0 g of polyvinylpyrrolidone with 45 ml of purified water is completely dissolved, a 10% solution of polyvinylpyrrolidone is prepared, used as a humectant to increase the adhesion between the particles of the components of the tabletting mixture.

Separate screening of methylethylpyridinol hydrochloride, a filler based on corn starch and pregelatinized starch (trademark StarCap 1500, registered by BPSI Holdings, LLC) and magnesium stearate is carried out through sieves with 0.15 mm openings. The sieved methylethylpyridinol hydrochloride (425.0 g), StarCap 1500 (25.5 g) and microcrystalline cellulose (127.5 g) are mixed for 30 minutes in a mixer having sigmoid-shaped blades. The resulting mass in the same mixer is moistened with a 10% solution of polyvinylpyrrolidone (3 × 10 ml) with constant stirring until the moisture is evenly distributed. The moistened mass is granulated by passing through a granulator with a hole size of 1.0 mm.

Wet granules are dried in an oven at a temperature of 40 ° C until a residual moisture content of 2.0-3.5% is reached. The dried granules are then subjected to dry granulation, for which they are passed through a granulator with a hole size of 1.0 mm, and then dusted for 10 minutes using magnesium stearate (3.4 g, 1% of the total mass) to improve the fluidity of the granules and reduce their sticking together.

The granules obtained are pressed into 0.350 g tablets in a Korsch tablet press equipped with spherical punches. The resulting tablets are dedusted on a metal sieve with a hole size of 3-4 mm. The mass of the obtained tablet cores is 490.0 g (approximately 1400 tablets).

Coating on tablet cores begins with the preparation of a 20% suspension of an integrated coating system based on polyvinyl acetate (Opadry trademark registered by BPSI Holdings, LLC). Opadry powder (15.0 g) is added to 60 ml of purified water with vigorous stirring in portions, preventing its accumulation in volume. The coating suspension is stirred for 15-20 minutes, and then filtered through a nylon sieve No. 23.

The tablet cores are coated in a drum-type apparatus under the conditions indicated below. Inlet air temperature: 30 ± 2 ° С, outlet air temperature: 28 ± 1 ° С, pressure: 2.5 ± 0.5 bar, coating suspension flow rate through the nozzle: 8 + 1 ml / min, preliminary heating of the cores: 10 min to 45-50 ° С, suspension spraying time: 30-40 min, final drying of nuclei - 10 min. The coating process is carried out to obtain a mass gain of 3-5%.

The finished coated tablets are packed in blisters (10 pieces each) or in polymer jars with a screw neck and a screw-on lid for medicines and vitamins (30 pieces each). The packaging is labeled to identify the drug and directions for use are applied.

Table 5 shows the absolute and relative composition of the tablet.

Table 5 Name of components Content in one capsule g % Methyl ethyl pyridinol hydrochloride 0.25 70.8 Microcrystalline cellulose 0,075 21,2 Based filler starch (StarCap 1500) 0.015 4.2 Polyvinylpyrrolidone 0.002 0.6 Magnesium stearate 0.002 0.6 Opadry Coating Compound 0.009 2.5 Tablet weight 0.390 100.0

Example 8. Determining the compliance of the obtained tablets with the requirements of the State Pharmacopoeia of the Russian Federation.

A representative sample is formed from a batch of tablets and studies of physicochemical properties are carried out in accordance with the instructions of the State Pharmacopoeia of the Russian Federation (GF XI), the references to which are given in table 6.

Table 6 Indicator Norm Test method Average weight 0.337-0.373 g GF XI, issue 2, p. 154 Deviation from 18/20: ± 7.5% GF XI, issue 2, p. 154 medium weight 2/20: ± 15% Disintegration no more than 15 minutes GF XI, issue 2, p. 154 Homogeneity 10/10: ± 15% or UV spectrophotometry dosing 28/30: ± 15% 0/30: no more than ± 25% Foreign matter no more than 1,5% HPLC Microbiological purity Category 3A GF XI, issue 2, p. 193 and amend. No.2 of 01/01/2002 Quantitative content 0.231-0.269 g (0.25 ± 7.5%) UV spectrophotometry

As a result of studies of samples from batches of tablets obtained in accordance with examples 4-6, it was found that the batches satisfy the requirements of the Publication XI of the State Pharmacopoeia of the Russian Federation.

Example 9. The establishment of compliance of the obtained tablets with the requirements for drugs during storage

The preparation “Emoxipin, coated tablets, 250 mg” was stored in tightly closed polymer jars at a temperature of 25 ± 5 ° C and a relative humidity of 75 75 ± 10%. Every six months, one can of each series of the drug was opened and 10 randomly selected tablets were evaluated for compliance with the requirements 1-9 listed below.

Requirement 1 - Description: Biconvex-coated orange tablets. On the cross section, two layers are visible - the inner (core) white and the outer (thin shell) orange.

Requirement 2 - Authenticity: Certified by UV spectrophotometry and thin layer chromatography (TLC).

Requirement 3 - Average weight and deviation from the average weight of the contents of the tablets: from 0.297 to 0.397 g.

Requirement 4 - Disintegration: not more than 20 '(minutes).

Requirement 5 - Dissolution: At least 75% methylethylpyridinol hydrochloride must pass into the solution after 45 minutes.

Requirement 6 - Impurities: not more than 0.5% (TLC).

Requirement 7 - Mass loss on drying: not more than 2.0%.

Requirement 8 - Microbiological purity: the preparation must be microbiologically pure.

Requirement 9 - Quantification of the active substance: 0.18 to 0.30 g.

Evaluations of tablet samples taken from 3 different lots for compliance with requirements 1-9 are shown in Table 7.

The above data show that the preparation "Emoxipin, coated tablets, 250 mg" obtained in accordance with the present invention has a shelf life of 5 years.

Claims (3)

1. A solid, individual dosage form in the form of a tablet, having a pronounced antistress, moderate tranquilizing, nootropic, antiamnestic and antihypoxic effect, comprising as an active component an effective amount of 2-ethyl-6-methyl-3-pyridin-3-ol hydrochloride and pharmaceutically acceptable excipients, characterized in that it contains 65.0-92.5 wt.% 2-ethyl-6-methyl-3-pyridin-3-ol hydrochloride, 25.6-2.5 wt.% calcium phosphate disubstituted as a filler, 0.4-1.9 wt.% oxypro iltsellyulozy as a binder and 9,0-0,6 wt.% of substances providing fluidity and prevent sticking. 2. The dosage form according to claim 1, characterized in that the tablet is coated with an Opadry shell based on polyvinyl acetate, and the weight of the shell is not more than 2.5% by weight of the dosage form. 3. The method of obtaining a solid individual dosage form according to claim 1 or 2, characterized in that when it is carried out
1) prepare purified water to perform all technological and auxiliary operations that meets all the requirements of current regulatory documents,
2) prepare a humidifier solution containing 5-10 wt.% A binder that increases the adhesion between the particles of the components of the tablet mixture,
3) separate sifting of methyl ethyl pyridinol hydrochloride and, if necessary, auxiliary substances, such as fillers, through sieves with openings of 0.10-0.25 mm,
4) sifted methylethylpyridinol hydrochloride and fillers are mixed until a homogeneous mass is obtained,
5) moisten the resulting mass with a humidifier solution until the moisture distribution is even,
6) the moistened mass is granulated,
7) the wet granules are dried at a temperature of 40-50 ° C until a residual moisture content of 1.5-4.0% is reached,
8) the dried granules are subjected to dry granulation and dusting with a substance that improves the fluidity of the granules and reduces their adhesion,
9) the obtained granules are pressed into tablets, which are then dedusted and optionally coated with a tablet core temperature of 30 to 50 ° C, an inlet temperature of the apparatus of 50 to 80 ° C and a relative humidity of less than 50%, and
10) ready-made individual dosage forms in the form of tablets are packaged, and a label is applied to the packaging to identify the drug, and directions for use are applied.