UA146306U - METHOD OF PREPARATION OF MEDICINAL PRODUCT IN SOLID DOSAGE FORM - Google Patents

Abstract

A method of manufacturing a drug in solid dosage form includes mixing such components of the drug as a polycyclic pyridone derivative of General structural formula (I) and excipients. As a polycyclic pyridone derivative of General structural formula (I) use a polycyclic pyridone derivative of structural formula (II). (II) Microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide, magnesium stearate are used as excipients. Before mixing the components of the drug, sieve each of the components of the drug through a vibrating screen. Mixing of the sieved components of the drug is carried out to obtain a mixture containing the following ratio of components, wt. %: polycyclic pyridone derivative of structural formula (II) 12-14 microcrystalline cellulose 47-53 lactose monohydrate 24-30 crospovidone 5-9 colloidal silicon dioxide 0.4-1.6 magnesium stearate 0.8-3. After mixing the components of the drug, the mixture is granulated to obtain granules and compressed into a portion of granules to obtain a tablet.

Description

of the medicinal product, each of the components of the medicinal product is sifted through a vibrating sieve. Mixing of the sifted components of the medicinal product is carried out to obtain a mixture containing the following ratio of components, wt. 90: polycyclic pyridone derivative of structural 12-14 formula (II) microcrystalline cellulose 47-53 lactose monohydrate 24-30 crospovidone 5-9 colloidal silicon dioxide 0.4-1.6 magnesium stearate 0.8-3.

After mixing the components of the medicinal product, the mixture is granulated to obtain granules and a weight of granules is pressed to obtain a tablet.

The utility model belongs to the field of medicine, namely to methods of manufacturing solid dosage form drugs for the treatment of acute respiratory viral infections.

Acute respiratory viral infections (hereinafter abbreviated ARVI) are the most common human disease affecting people in all countries. According to WHO, adults usually get SARS from two to five times a year, children can get sick from six to ten times a year, and schoolchildren - even up to twelve times a year. The probability of symptomatic infections increases with age - the human immune system weakens in old age.

ARVI is a group of viral infections characterized by a general intoxication syndrome and damage to the mucous membrane of the respiratory tract. A significant number of pathogens (more than 200) are known that belong to various nosological groups of viral nature (influenza, parainfluenza viruses, adenoviruses, respiratory syncytial viruses, coronaviruses, picornaviruses, rhinoviruses, enteroviruses, herpes viruses, etc.), which are linked by " area" of affected organs - the human respiratory system.

The clinical picture of SARS is characterized by an acute onset, fever, moderately pronounced symptoms of intoxication, which develop in the first 2-3 days of the disease (headache, decreased appetite, lethargy, adynamia, less often - vomiting); catarrhal symptoms (nasal congestion, nasal discharge, often abundant, sore throat, hyperemia of the pharynx, hyperemia and granularity of the back wall of the pharynx, pharyngitis, tonsillitis, possible hoarseness, dry or expectorant cough, hyperemia of the conjunctiva).

The most common cause of SARS is rhinovirus (from 3 to 80 95 cases).

Rhinovirus is an RNA-containing virus in the picornavirus family. Currently, 99 types of viruses belonging to this family are known. The coronavirus is the cause of 10 to 15 95 cases of SARS. The flu virus (influenza) causes 5 to 15 95 cases. Other cases of diseases can occur as a result of infection with human parainfluenza viruses, respiratory syncytial virus, adenoviruses, enteroviruses, and metapneumovirus.

Adenovirus infection is characterized by a variety of clinical forms of the disease: pharyngoconjunctival fever, primary adenovirus pneumonia and catarrh of the respiratory tract, intestinal form, mesoadenitis, damage to lymphoid tissue, liver, spleen.

Rhinovirus infection begins acutely and is manifested either by catarrh of the upper respiratory tract, or by its combination with intestinal disorders.

Respiratory syncytial infection is characterized by a significant frequency of bronchiolitis, pneumonia with asthmatic syndrome and the development of respiratory failure. In older children, a respiratory infection is usually manifested by catarrh of the respiratory tract against the background of moderate phenomena of general intoxication.

Infection with the influenza virus leads to an acute disease characterized by intoxication, catarrhal phenomena from the upper respiratory tract. Clinical manifestations of rhinitis, pharyngitis, laryngitis, tracheitis and bronchitis are observed. With a mild form of the disease, the body temperature remains normal or rises to subfebrile numbers, symptoms of intoxication are weak or absent. In the case of moderate flu, the temperature rises to 38.5-39.5 "С, classical symptoms of the disease are added: intoxication (profuse sweating, weakness, pain in muscles and joints, headache), catarrhal symptoms, respiratory symptoms (runny nose, cough , hyperemia of the face, dryness in the nasal cavity, sore throat).With a severe form of flu, the body temperature rises to 40 "C, in addition to the above symptoms, convulsions, hallucinations, nosebleeds, vomiting may appear.

Unlike influenza, parainfluenza is characterized by a gradual onset, less pronounced phenomena of general intoxication, a more benign course, a less pronounced, but often longer (up to 7 days) febrile reaction. With parainfluenza, the mucous membrane of the larynx is also involved in the inflammatory process. Therefore, clinically expressed symptoms of laryngitis are a frequent symptom of parainfluenza. In children, parainfluenza can be accompanied by stenosing laryngitis - croup.

As you can see, the flu is one of the most serious diseases among SARS in terms of symptoms and course of the disease.

There is no effective treatment for SARS, except for the flu; treatment of diseases is aimed at easing the course of the disease.

Influenza (English ipYasepla, French aogirre) is an acute viral infectious disease from the SARS group, the special characteristic of which is the periodic epidemic or even pandemic nature of its spread. Influenza has symptoms similar to other SARS, but the consequences of influenza are much more dangerous than other SARS. Therefore, the first signs of damage to the respiratory system require special attention because it is the flu that needs to be detected. The most common complication of flu is hemorrhagic pulmonary edema, cerebral edema, which can lead to the patient's death in just a few days. Heart failure also often develops as a result of the flu, often worsening the course of underlying heart diseases. Frequent complications are the addition of a bacterial infection in the form of bronchitis or pneumonia.

According to the classification of viruses, the influenza virus belongs to the RNA viruses of the orthomyxovirus family (lat.

Ogpipotuhomigiidae) and includes three serotypes A, B, C.

Influenza diseases spread among people in the form of epidemics that occur every 2-3 years, characterized by pronounced seasonality of influenza - winter, early spring, and pandemics. In the 20th century, humanity experienced three influenza pandemics. As a result of the most widespread of them - the epidemic of the so-called Spanish flu of 1918 - according to estimates, from 50 to 100 million people died. As a result of the pandemics of 1957 and 1968, one to two million people died.

Today, the situation is such that the common seasonal flu virus causes up to 500,000 deaths each year, with about 36,000 deaths in the United States alone. Elderly people are especially vulnerable to the flu. According to US statistics, people aged 65 and older die from the flu much more often than people of other ages: this age group accounts for up to 89 95 of all flu-related deaths.

The World Health Organization indicates that there are currently only two drugs against the influenza virus based on such chemical compounds that belong to the class of neuraminidase inhibitors of the influenza virus - such compounds are Zanamivir and Oseltamivir.

Such an antiviral pharmaceutical composition is known under the trade name RELENTSA (information in the article on the web page at the address пирз//сотрепайт.сот.ца/дес/270268/), which is produced in such a dosage form as a dosed powder for inhalation and which contains as an active pharmaceutical ingredient a chemical compound with an international non-proprietary name

Zanamivir contains pharmaceutically acceptable excipients.

Zanamivir is a synthetic chemical compound developed for the treatment of influenza, having the structural formula:

But- On oh no SHK

NM about n.u"

MH belongs to the group of compounds that are neuraminidase inhibitors of the influenza virus, which prevent

On the multiplication of the influenza virus and its spread in the human body.

RELENTSA is used by inhaling the pharmaceutical composition through the mouth - the composition settles on the surface of the tissues of the respiratory system organs in high concentrations.

The disadvantage of RELENTS is the low bioavailability of the active pharmaceutical ingredient of the pharmaceutical composition - when the pharmaceutical composition is inhaled, the bioavailability of Zanamivir is 10-20 95. Research has established that the bioavailability

Zanamivir after oral administration is only 2 9.

Another disadvantage of RELENTS is that to achieve the effect of treatment from the application

RELENZA, the application should be started within the first 48 hours from the appearance of the first symptoms of the disease. In case of a delay in starting the application, the treatment may not have an effect. There are also problems when using RELENZA in such a group of patients as patients with respiratory tract diseases - such patients must have fast-acting inhaled bronchodilators as a means of first aid in cases of unwanted effects on the functions of the respiratory system.

In addition, strains of influenza A virus resistant to Zanamivir were found in 2011, including in people who were not treated with RELENZA.

From the European invention application EP 3290424 JSC (publ. 07.03.2018), such chemical compounds as polycyclic pyridone derivatives of the general structural formula (I) are known

here about

J. M. also a and

Ba in and (in and I and

She x. re ee

Bey and Khoat - Zh, which have an antiviral effect and can be used for the treatment of ARVI, in particular, the flu.

The advantages of the described polycyclic derivatives of pyridone of the general structural formula (I) are high efficiency of action against RNA viruses, in particular against the influenza virus - sometimes one dose of a chemical compound within 48 hours after infection of the body with a virus is enough to stop the replication of the virus in cells. In the description of the European application for the invention EP 3290424 A1, examples of the implementation of medicinal products based on the specified polycyclic pyridone derivatives are described, and methods of manufacturing medicinal products are described, in particular, methods of manufacturing medicinal products in solid dosage forms are described. Thus, on page 95 of the European application for the invention EP 3290424 A1, a method of manufacturing a medicinal product in such a solid dosage form as tablets is described - the method includes mixing a chemical compound, which is a polycyclic pyridone derivative of the general structural formula (I), and such auxiliary substances as lactose and calcium stearate, grinding the resulting mixture, granulating the mixture to obtain granules, drying the obtained granules, adding calcium stearate to the granules, pressing the mixture to obtain tablets.

The disadvantage of the known method of manufacturing a medicinal product in a solid dosage form is the low physico-chemical properties of the obtained medicinal forms - the obtained tablets can easily crumble under small loads. In addition, the resulting tablets are inconvenient to swallow.

The useful model is based on the task of improving the method of manufacturing a medicinal product in a solid dosage form by changing the actions in the manufacturing method of the medicinal product and changing the components in the composition of the medicinal product, due to which the obtained solid dosage forms of the medicinal product have higher physicochemical properties; expand the arsenal and assortment of medicines for the treatment of ARVI, in particular, influenza.

The problem is solved by the fact that in the method of manufacturing a medicinal product in a solid dosage form, which includes mixing such components of the medicinal product as a polycyclic pyridone derivative of the general structural formula (I)

OV oo

Shield them

IS; Из и и З ш на на я ш Ш Ю ва Я ne ker r ta excipients, according to a useful model, as a polycyclic derivative of pyridone

From the general structural formula (I), a polycyclic derivative of pyridone of the structural formula (II) is used. TV

A p Yany -- M i y M

Kk AK Same approx. and A-6.

Gaya How! ; (I) microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide, magnesium stearate are used as auxiliary substances, before mixing the components of the medicinal product, each of the components of the medicinal product is sieved through a vibrating sieve, the sifted components of the medicinal product are mixed to obtain a mixture containing the following ratio of components, mass 9o: polycyclic pyridone derivative of the structural formula (II) 12-14 microcrystalline cellulose 47-53 lactose monohydrate 24-30 crospovidone 5-9 colloidal silicon dioxide 0.4-1.6 magnesium stearate 0.8-3, after mixing the components of the medicinal product perform granulation of the mixture to obtain granules and pressing of a weight of granules to obtain a tablet.

In addition, according to one of the variants of the implementation of the useful model, the method additionally includes applying to the tablet a solution containing a film-forming agent, drying the applied solution to form a shell on the tablet.

In addition, according to one of the variants of the implementation of the useful model, ORAYUKU UUNITE OZA48081 is used as a film-forming agent.

In addition, according to one of the variants of the implementation of the useful model, the mixture, which is obtained after mixing the sifted components of the drug, contains the following ratio of components, wt. 9: polycyclic pyridone derivative of structural formula (II) 13-13.6 microcrystalline cellulose 50-51.5 lactose monohydrate 26-27.5 crospovidone 6-7.5 colloidal silicon dioxide 0.7-1.3 magnesium stearate 1.3 -2.

In addition, according to one of the variants of the implementation of the useful model, the tablet contains a polycyclic pyridone derivative of the structural formula (II) in an amount from 10 to 50 mg.

A useful model is explained by examples.

EXAMPLE 1

Stage 1. Sifting. The polycyclic derivative of pyridone of the structural formula (I), microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide is sieved through a 40-mesh vibrating sieve until complete passage, and magnesium stearate is sieved through a 60-mesh vibrating sieve until complete passage. The integrity of the sieve is checked before and after sieving individual components. Each ingredient is sifted separately to prevent cross-contamination and mixing with other products.

Stage 2. Mixing. 4700 g of screened microcrystalline cellulose, 500 g of crospovidone and 40 g of colloidal silicon dioxide are placed in any suitable mixer-granulator and mixed at low speed for 10 minutes to obtain a homogeneous dry mixture.

In a reactor with a steam jacket, heat 6500 ml of purified water to a temperature of 60 °C. Add 2400 g of sifted lactose monohydrate to water heated to 60 °C and continuously stir until a homogeneous solution is obtained. The obtained homogeneous solution is passed into

From the clean reactor through a 120 mesh nylon cloth, after which it is cooled to a temperature of 37 76.

Stage 3. Granulation. The homogeneous solution is injected into a mixer-granulator containing a homogeneous dry mixture and mixed for 10 minutes to obtain wet granules.

Wet granules are placed in a fluidized bed dryer and primary drying is carried out at a temperature of 65 "C for 30 minutes to obtain dried granules. The dried granules are sieved through a 12-mesh sieve. If necessary, too large granules are crushed and after grinding they are sieved through a 12-mesh sieve until all the granules will not pass through the sieve. The granules are then subjected to final drying in any suitable drying equipment with an initial temperature of 65 "C and a final temperature of 38 "C for 30 minutes. The moisture content of the granules should not exceed 3.0 95 wt.

The pellets are loaded into any suitable mixer, such as an octagonal mixer. After that, 1200 g of sieved polycyclic pyridone derivative of structural formula (III) and 80 g of magnesium stearate are loaded and mixed for 15 minutes until lubricated granules are obtained.

Stage 4. Pressing the granules to obtain a tablet. Lubricated granules are compressed into tablets using any acceptable tablet machine.

Stage 5. Applying a solution containing a film-forming agent to the tablet. 2300 ml of purified water and 200 g of film-forming agent ORAOKU MUNITE are loaded into the reactor

OZA48081 and mix until a homogeneous solution is obtained. Tablets are coated with the resulting homogeneous solution in any suitable equipment, for example, in a coating boiler.

Stage 6. Drying of the applied solution with the formation of a shell on the tablet. Tablets covered with a homogeneous solution are blown with an air jet in any suitable drum, for example, in a coating boiler, which was used to coat the tablets with a solution.

EXAMPLE 2

Stage 1. Sifting. The polycyclic derivative of pyridone of the structural formula (I), microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide is sieved through a 40-mesh vibrating sieve until complete passage, and magnesium stearate is sieved through a 60-mesh vibrating sieve until complete passage. The integrity of the sieve is checked before and after sieving individual components. Each ingredient is sifted separately to prevent cross-contamination and mixing with other products.

Stage 2. Mixing. 5000 g of screened microcrystalline cellulose, 600 g of crospovidone and 70 g of colloidal silicon dioxide are placed in any suitable mixer-granulator and mixed at low speed for 10 minutes to obtain a homogeneous dry mixture.

In a reactor with a steam jacket, 6990 ml of purified water is heated to a temperature of 60 °C. 2600 g of sifted lactose monohydrate is added to water heated to 60 °C and continuously stirred until a homogeneous solution is obtained. The obtained homogeneous solution is passed into a clean reactor through a 120-mesh nylon cloth, after which it is cooled to a temperature of 37 76.

Stage 3. Granulation. The homogeneous solution is injected into a mixer-granulator containing a homogeneous dry mixture and mixed for 10 minutes to obtain wet granules.

Wet granules are placed in a fluidized bed dryer and primary drying is carried out at a temperature of 65 "C for 30 minutes to obtain dried granules. The dried granules are sieved through a 12-mesh sieve. If necessary, too large granules are crushed and after

The grinding is sifted through a 12-mesh sieve until all the granules pass through the sieve. The granules are then subjected to final drying in any suitable drying equipment with an initial temperature of 65 °C and a final temperature of 38 °C for 30 minutes. The moisture content in the granules should not exceed 3.0 95 wt.

The pellets are loaded into any suitable mixer, such as an octagonal mixer. After that, 1300 g of sieved polycyclic pyridone derivative of structural formula (II) and 130 g of magnesium stearate are loaded and mixed for 15 minutes until lubricated granules are obtained.

Stage 4. Pressing the granules to obtain a tablet. Lubricated granules are compressed into tablets using any acceptable tablet machine.

Stage 5. Applying a solution containing a film-forming agent to the tablet. 3125 ml of purified water and 250 g of film-forming agent ORAOKMU UUNITE are loaded into the reactor

OZA48081 and mix until a homogeneous solution is obtained. Tablets are coated with the resulting homogeneous solution in any suitable equipment, for example, in a coating boiler.

Stage 6. Drying of the applied solution with the formation of a shell on the tablet. Tablets covered with a homogeneous solution are blown with an air jet in any suitable drum, for example, in a coating boiler, which was used to coat the tablets with a solution.

EXAMPLE Z

Stage 1. Sifting. The polycyclic derivative of pyridone of the structural formula (I), microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide is sieved through a 40-mesh vibrating sieve until complete passage, and magnesium stearate is sieved through a 60-mesh vibrating sieve until complete passage. The integrity of the sieve is checked before and after sieving individual components. Each ingredient is sifted separately to prevent cross-contamination and mixing with other products.

Stage 2. Mixing. 5075 g of screened microcrystalline cellulose, 675 g of crospovidone and 70 g of colloidal silicon dioxide are placed in any suitable mixer-granulator and mixed at low speed for 10 minutes to obtain a homogeneous dry mixture.

In a reactor with a steam jacket, heat 7190 ml of purified water to a temperature of 60 °C, then add 2675 g of sifted lactose monohydrate to water heated to 60 °C and continuously stir until a homogeneous solution is obtained. The obtained homogeneous solution is passed into a clean reactor through a 120-mesh nylon cloth, after which it is cooled to a temperature of 37 76.

Stage 3. Granulation. The homogeneous solution is injected into a mixer-granulator containing a homogeneous dry mixture and mixed for 10 minutes to obtain wet granules.

Wet granules are placed in a fluidized bed dryer and primary drying is carried out at a temperature of 65 "C for 30 minutes to obtain dried granules. The dried granules are sieved through a 12-mesh sieve. If necessary, too large granules are crushed and after grinding they are sieved through a 12-mesh sieve until all the granules will not pass through the sieve. The granules are then subjected to final drying in any suitable drying equipment with an initial temperature of 65 "C and a final temperature of 38 "C for 30 minutes. The moisture content of the granules should not exceed 3.0 95 wt.

The pellets are loaded into any suitable mixer, such as an octagonal mixer. After that, 1330 g of sifted polycyclic pyridone derivative of the structural formula (II) and 165 g of magnesium stearate are loaded and mixed for 15 minutes to obtain lubricated granules.

Stage 4. Pressing the granules to obtain a tablet. Lubricated granules are compressed into tablets using any acceptable tablet machine.

Stage 5. Applying a solution containing a film-forming agent to the tablet. 3440 ml of purified water and 275 g of film-forming agent ORAYUKU UMNITE are loaded into the reactor

OZA48081 and mix until a homogeneous solution is obtained. Tablets are coated with the resulting homogeneous solution in any suitable equipment, for example, in a coating boiler.

Stage 6. Drying of the applied solution with the formation of a shell on the tablet. Tablets covered with a homogeneous solution are blown with an air jet in any suitable drum, for example, in a coating boiler, which was used to coat the tablets with a solution.

EXAMPLE 4

Stage 1. Sifting. The polycyclic derivative of pyridone of the structural formula (I), microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide is sieved through a 40-mesh vibrating sieve until complete passage, and magnesium stearate is sieved through a 60-mesh vibrating sieve until complete passage. The integrity of the sieve is checked before and after sieving individual components. Each ingredient is sifted separately to prevent cross-contamination and mixing with other products.

Stage 2. Mixing. 5150 g of screened microcrystalline cellulose, 750 g of crospovidone and 130 g of colloidal silicon dioxide are placed in any suitable mixer-granulator and mixed at low speed for 10 minutes to obtain a homogeneous dry mixture.

In a reactor with a steam jacket, heat 7390 ml of purified water to a temperature of 60 °C. 2750 g of sifted lactose monohydrate is added to water heated to 60 °C and continuously stirred until a homogeneous solution is obtained. The obtained homogeneous solution is passed into a clean reactor through a 120-mesh nylon cloth, after which it is cooled to a temperature of 37 76.

Stage 3. Granulation. The homogeneous solution is injected into a mixer-granulator containing a homogeneous dry mixture and mixed for 10 minutes to obtain wet granules.

Wet granules are placed in a fluidized bed dryer and primary drying is carried out at a temperature of 65 "C for 30 minutes to obtain dried granules. The dried granules are sieved through a 12-mesh sieve. If necessary, oversized granules are crushed and, after grinding, sieved through a 12-mesh sieve until all the granules will not pass through the sieve. The granules are then subjected to final drying in any suitable drying equipment with an initial temperature of 65 "C and a final temperature of 38 "C for 30 minutes. The moisture content of the granules should not exceed 3.0 95 wt.

The pellets are loaded into any suitable mixer, such as an octagonal mixer. After that, 1360 g of sifted polycyclic pyridone derivative of the structural formula (I) and 200 g of magnesium stearate are loaded and mixed for 15 minutes to obtain lubricated granules.

Stage 4. Pressing the granules to obtain a tablet. Lubricated granules are compressed into tablets using any acceptable tablet machine.

Stage 5. Applying a solution containing a film-forming agent to the tablet. 3750 ml of purified water and 300 g of film-forming agent ORAYUKU MNITE bo OZA48081 are loaded into the reactor and mixed until a homogeneous solution is obtained. Tablets are covered with the obtained (c;

homogenous solution in any suitable equipment, for example in a dredge boiler.

Stage 6. Drying of the applied solution with the formation of a shell on the tablet. Tablets covered with a homogeneous solution are blown with an air jet in any suitable drum, for example, in a coating boiler, which was used to coat the tablets with a solution.

EXAMPLE 5

Stage 1. Sifting. The polycyclic derivative of pyridone of the structural formula (II), microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide is sieved through a vibrating sieve of 40 mesh until complete passage, and magnesium stearate is sieved through a vibrating sieve of 60 mesh until complete passage. The integrity of the sieve is checked before and after sieving individual components. Each ingredient is sifted separately to prevent cross-contamination and mixing with other products.

Stage 2. Mixing. 5300 g of screened microcrystalline cellulose, 900 g of crospovidone and 160 g of colloidal silicon dioxide are placed in any suitable mixer-granulator and mixed at low speed for 10 minutes to obtain a homogeneous dry mixture.

In a reactor with a steam jacket, 8065 ml of purified water is heated to a temperature of 60 °C.

3000 g of sifted lactose monohydrate is added to water heated to 60 C and continuously stirred until a homogeneous solution is obtained. The obtained homogeneous solution is passed into a clean reactor through a 120-mesh nylon cloth, after which it is cooled to a temperature of 37 76.

Stage 3. Granulation. The homogeneous solution is injected into a mixer-granulator containing a homogeneous dry mixture and mixed for 10 minutes to obtain wet granules.

Wet granules are placed in a fluidized bed dryer and primary drying is carried out at a temperature of 65 "C for 30 minutes to obtain dried granules. The dried granules are sieved through a 12-mesh sieve. If necessary, oversized granules are crushed and, after grinding, sieved through a 12-mesh sieve until all the granules will not pass through the sieve. The granules are then subjected to final drying in any suitable drying equipment with an initial temperature of 65 "C and a final temperature of 38 "C for 30 minutes. Contents

Of moisture in the granules should not exceed 3.0 95 wt.

The pellets are loaded into any suitable mixer, such as an octagonal mixer. After that, 1400 g of sieved polycyclic pyridone derivative of structural formula (II) and 300 g of magnesium stearate are loaded and mixed for 15 minutes to obtain lubricated granules.

Stage 4. Pressing the granules to obtain a tablet. Lubricated granules are compressed into tablets using any acceptable tablet machine.

Stage 5. Applying a solution containing a film-forming agent to the tablet. 4375 ml of purified water and 350 g of film-forming agent ORAOKMU UUNITE are loaded into the reactor

OZA48081 and mix until a homogeneous solution is obtained. Tablets are coated with the resulting homogeneous solution in any suitable equipment, for example, in a coating boiler.

Stage 6. Drying of the applied solution with the formation of a shell on the tablet. Tablets covered with a homogeneous solution are blown with an air jet in any suitable drum, for example, in a coating boiler, which was used to coat the tablets with a solution.

The given examples only illustrate a useful model and do not limit It in any way.

The technical result, which is achieved when applying the useful model: - the method allows to manufacture a medicine in a dosage form, which is characterized by the best physico-chemical properties. In particular, the dosage forms according to the useful model are characterized by less fragility and, at the same time, better swelling and disintegration due to the use of crospovidone instead of the combination of povidone and croscarmellose sodium to obtain the dosage forms. In addition, the method makes it possible to produce a medicinal product in a dosage form, which is characterized by better physico-chemical properties due to the use of colloidal silicon dioxide, which increases the stability of dosage forms during storage, contributes to better pressing of granules and obtaining dosage forms with optimal physico-chemical properties; - the method makes it possible to expand the arsenal and assortment of medicines for the treatment of SARS, in particular, influenza, by obtaining a medicine in a solid dosage form, which is characterized by better physicochemical properties compared to known medicinal 60 means;

- additionally, the method makes it possible to produce a medicinal product in a dosage form, which is characterized by more convenient use due to the presence of a film coating, which masks the taste and smell of the medicinal product, and also facilitates easier swallowing of the dosage form.

Claims (5)

USEFUL MODEL FORMULA 1. The method of manufacturing a medicinal product in a solid dosage form, which includes mixing such components of the medicinal product as a polycyclic pyridone derivative of the general structural formula (I) and auxiliary substances, which differs in that as a polycyclic derivative of pyridone of the general structural formula (I) a polycyclic derivative of pyridone of the structural formula (II) is used. i se i Y mes u EE sht Her preg ny o still And ; (I) microcrystalline cellulose, lactose monohydrate, crospovidone, colloidal silicon dioxide, magnesium stearate are used as auxiliary substances, before mixing the components of the medicinal product, each of the components of the medicinal product is sieved through a vibrating sieve, the sifted components of the medicinal product are mixed to obtain a mixture containing the following ratio of components, mass 9o: polycyclic pyridone derivative of the structural formula (II) 12-14 microcrystalline cellulose 47-53 lactose monohydrate 24-30 crospovidone 5-9 colloidal silicon dioxide 0.4-1.6 magnesium stearate 0.8-3, after mixing the components of the medicinal product perform granulation of the mixture to obtain granules and pressing of a weight of granules to obtain a tablet. 2. The method according to claim 1, which is characterized by the fact that it additionally includes applying to the tablet a solution containing a film-forming agent, drying the applied solution with the formation of a shell on the tablet. 3. The method according to claim 2, which differs in that ORAOAMU M/NITE OZA48081 is used as a film-forming agent. 4. The method according to any of claims 1-3, which is characterized by the fact that the mixture obtained after mixing the components of the medicinal product contains the following ratio of components, wt. Fo: polycyclic pyridone derivative of structural formula (II) 13-13.6 microcrystalline cellulose 50-51.5 lactose monohydrate 26-27.5 crospovidone 6-7.5 colloidal silicon dioxide 0.7-1.3 magnesium stearate 1.3 -2. 5. The method according to any one of claims 1-4, which is characterized by the fact that the tablet contains a polycyclic pyridone derivative of the structural formula (II) in an amount from 10 to 50 mg.