RU2349334C2 - Medicine of sedative and antispasmodic effect and method of preparation (versions) - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns medicine, particularly medical drugs with organic active components, medicines with sedative, vasodilating and antispasmodic effect, and methods of medicine obtainment, an can be applied in treatment of neuroses with high irritability, increased agitation, insomnia, neurocirculation dystonia, early stage of hypertension, non-acute cardiovascular spasm, digestive organ spasms related to neurovegetative disorders. Medicine of sedative and antispasmodic effect includes ethyl ether of α-bromisovaleric acid, Phenobarbital, peppermint oil, microcrystalline cellulose auxiliary substances for solid formulation obtainment in pellet form at the following component ratio, wt %: ethyl ether of α-bromisovaleric acid 1.37-8.2; Phenobarbital 1.25-7.5; peppermint oil 0.16-0.58; microcrystalline cellulose 2-15; the rest is auxiliary substances; pellets are covered with shell composed of β-cyclodextrin in amount of 10% of dry coating weight. First version of method of obtaining medicine with sedative and antispasmodic effect involves initial mixing of ethyl ether of α-bromisovaleric acid with peppermint oil, so that the mix comprises over 4.5% of total pellet, core pellet or capsule content weight, adding the mix to humid β-cyclodextrin taken in amount of up to 70% of total pellet core weight, stirring for 1-2 minutes, drying and pelletising of obtained mix, mixing granulate with Phenobarbital and microcrystalline cellulose powders and auxiliary filler, fluffer and slider substances, pellet compression and coating with shell containing β-cyclodextrin in amount of up to 10% of dry coating weight. Second version of method involves initial mixing Phenobarbital with auxiliary filler substance, separate preparation of mix of ethyl ether of α-bromisovaleric acid with peppermint oil, so that the ether oil mix comprises less than 4.5% of total pellet, core pellet or capsule content weight, adding microcrystalline cellulose powder, powders with extensive crystal surface area, auxiliary fluffer and slider substances, adding obtained mix to Phenobarbital and filler mix, pellet compression and coating with shell containing β-cyclodextrin in amount of up to 10% of dry coating weight.

EFFECT: medicine of sedative and antispasmodic effect in solid pellet form, with sedative and antispasmodic action matching that of drops with similar effect, ensuring stability of volatile components.

20 cl, 8 ex, 11 tbl

Description

The invention relates to medicine, in particular to medicines containing organic active ingredients, and in particular to medicines exhibiting a sedative, vasodilating and antispasmodic effect, and methods for their preparation. The invention can be used to treat neurosis with increased irritability, increased irritability, insomnia, neurocirculatory dystonia, an early stage of hypertension, not pronounced spasm of the heart vessels, spasms of the digestive tract associated with neurovegetative disorders.

The increase in the number of neuroses, often combined with somatic pathology, in particular with diseases of the cardiovascular system, necessitates the improvement of existing and the creation of new drugs with complex effects for their treatment.

For the treatment of this pathology, as a rule, myotropic drugs (antispasmodics) are used, acting mainly on blood vessels, and neurotropic drugs acting on the nervous system - sedatives, hypnotics, tranquilizers.

Sedatives (sedatives) are divided into herbal and synthetic. Sedative herbal remedies are obtained from medicinal valerian, canine nettle, lemon balm, peppermint, passionflower. In particular, the rhizomes and roots of Valerian officinalis contain an essential oil, the main component of which is the ester of borneol and isovalerianic acid, as well as valerianic acid, borneol, organic acids, tannins, which exhibit a sedative and antispasmodic effect. Synthetic sedative drugs include bromide, barbiturates in small doses.

There are also combined drugs that have both antispasmodic and sedative effects.

Known combination drug "Valocordin" containing, g:

phenobarbital 2.0 ethyl bromoisovalerianate 2.0 peppermint oil 0.14 hop oil 0.02

Modern medicines. The latest reference. "Owl", St. Petersburg, - 2002, p.149-150].

Also known is a combined drug "Corvaldin", containing, g:

α-bromisovalerianic acid ethyl ester 20,0 phenobarbital 18.0 sodium hydroxide 3.15 peppermint oil 1.4 hop oil 0.2 ethyl alcohol 96% or   rectified ethyl alcohol 620 ml stabilizer 0.2 purified water up to 1.0 l

[Instructions for medical use of the drug, JSC "FARMAK", Kiev, Ukraine].

The effects of these drugs are determined by the active substances that make up their composition.

Ethyl α-bromisovalerianic acid, which is part of Corvaldin, is a sedative and antispasmodic and acts like an extract of valerian.

Phenobarbital, which is ingested when taking Corvaldin and Valocordin, has a mild sedative and vasodilating effect.

Peppermint oil, which has a reflex vasodilator and antispasmodic effect, is recommended for use with nervous agitation, insomnia, various neurotic conditions as a vasodilator in angina pectoris and diseases associated with spasms of the brain vessels.

Hop oil, which is part of Corvaldin and Valocordin, has a mild sedative effect. Ethyl bromisovalerianate, which is part of Valocordin, has a sedative antispasmodic effect.

Known tool for the prevention and treatment of pathology of the nervous and cardiovascular system - "Nikorval" containing, wt.%:

α-bromisovalerianic acid ethyl ester 0.5-3.0 phenobarbital 1.5-2.0 sodium hydroxide 0.2-0.4 peppermint oil 0.08-0.16 nifedipine 0.8-2.0 ethyl alcohol 96% 45-65 water 30-50

[Declaration Patent of Ukraine No. 32319, A61K 31/21, 1999].

Nifedipine, which is part of Nikorval, has a vasodilating and anti-ischemic effect, lowers blood pressure.

Closest to the claimed drug is the drug "Corvalol", which has a sedative, hypnotic and antispasmodic effect and containing, wt.%:

α-bromisovalerianic acid ethyl ester 2 phenobarbital 1.82 sodium hydroxide about 3 peppermint oil fourteen rectified ethyl alcohol and purified water up to 100

[Mashkovsky MD. Medicines. The New Wave, - 2001, vol. 1, p. 89].

The specified prototype, like all previous analogues, is available in the form of a solution and is used as drops with a small amount of water. However, the use of drops is not always convenient because of the impossibility of ensuring the exact dosage, indiscretion or inexperience of the patient preparing the drug, or its critical condition, or inconvenience when using the drug on the road. In addition, in the composition of Corvalol, ethyl alcohol of 96% was used to dissolve ethyl ester of α-bromisovalerianic acid, which, when used, leads to drying of the mucous membranes of the mouth and pharynx.

Due to the fact that the composition of Corvalol includes ethyl ester of α-bromisovalerianic acid, which is a liquid that is easily volatile and insoluble in water, until now it was not possible to create a solid dosage form in tablets or capsules on the basis of this substance. In addition, volatiles are not stable when stored. Corvalol contains a potent substance - phenobarbital, and when dosing with drops it is impossible to ensure the accuracy of dosing of this substance. The dispensers that are supplied with the package give large errors in the volume of the same number of drops.

A known method of obtaining a cardiovascular preparation "Validol" by preliminary granulation of powdered sugar, drying granules, mixing dry granules with liquid menthyl ester of isovalerianic acid, mixing with calcium stearate and tabletting. In order to introduce a drug substance, icing sugar is granulated with water, mixed with isovalerianic acid methyl ester, then with calcium stearate and tabletted [Compendium. Medications. Morion, 2005 L-200].

To obtain tablets from this liquid substance, it is necessary that its amount does not exceed 4.88%, and at the same time there remain problems with the stability of the substance in this form.

Closest to the claimed method is the method of obtaining the drug "Nikorval", which consists in adding nifedipine in portions to the alcohol-containing ethyl mixer or flask and mixing thoroughly until it is completely dissolved. Then phenobarbital, sodium hydroxide and ethyl ester of α-bromisovalerianic acid are added in small portions to another mixer or flask with water and mixed until the components are completely dissolved. The resulting two solutions are mixed together to obtain a clear liquid [Declaration Patent of Ukraine No. 32319, A61K 31/21, 1999].

The specified method does not make it possible to transfer into the solid dosage form liquid components that are in the composition of the product, that is, tablets or capsules.

The basis of the invention is the task of creating a selection of components and their amount of the drug sedative and antispasmodic action of a solid form in the form of tablets or capsules, which in its sedative and antispasmodic action would correspond to drops of a similar action and ensure stability of volatile ingredients.

The second task, which is the basis of the invention, is to create due to the selection of the components of the modes and parameters, the sequence of steps in the technological cycle of a method for producing a solid form of a sedative and antispasmodic drug.

The first task is solved in that the sedative and antispasmodic drug containing ethyl ester of α-bromisovalerianic acid, phenobarbital and peppermint oil, according to the invention additionally contains microcrystalline cellulose, excipients for creating a solid dosage form in the form of tablets in the following ratio of components, wt.%:

α-bromisovalerianic acid ethyl ester 1.37-8.2 phenobarbital 1.25-7.5 peppermint oil 0.16-0.58 microcrystalline cellulose 2-15 Excipients rest,

moreover, the tablets are coated, which includes β-cyclodextrin in a dose of up to 10% of the weight of the dry coating.

The drug may optionally contain β-cyclodextrin in a dose of up to 70 wt.%.

The drug may additionally contain hop oil in a dose of 0.0229-0.09 wt.%.

The second task is solved in that in a method for the manufacture of a medicinal product of sedative and antispasmodic action, including mixing phenobarbital, ethyl ester of α-bromisovalerianic acid, peppermint oil with auxiliary substances, according to the invention, ethyl ester of α-bromisovalerianic acid and peppermint oil are first mixed, moreover, the amount of the mixture is more than 4.5% of the total weight of the tablet, core tablet or capsule content, the mixture is added to moistened β-cyclodextrin, the amount of which is up to 70% by weight of the total weight of the tablet core, is mixed for 1-2 minutes, the resulting mixture is dried, granulated, after which the granulate is mixed with powders of phenobarbital, microcrystalline cellulose, excipients, disintegrants and glidants, tablets are pressed, and then they are coated with a membrane containing β-cyclodextrin in a dose of up to 10% of the weight of the dry coating.

Additionally, hop oil may be added.

In the process of coating, the tablets are heated and treated with heated air.

As fillers, lactose, starch, glycine, calcium diphosphate, calcium dihydrogen phosphate, glucose, sorbitol and / or mixtures thereof can be used.

As baking powder can use starch and its derivatives: crospovidone, croscarmellose and / or mixtures thereof.

Magnesium stearate, sodium fumarate, talc, polyvinylpyrrolidone and / or mixtures thereof can be used as glidants.

As the shell, a film, a sugar coating or combinations thereof can be used.

A film is made by mixing a film forming agent and a 1% β-cyclodextrin solution.

The sugar shell is made by mixing sugar, magnesium carbonate, aerosil, polyvinylpyrrolidone, titanium dioxide, talc and a solution of β-cyclodextrin or their derivatives or other components used in the industry for coating tablets.

The second task is also solved by the fact that in the method of manufacturing a medicinal product of sedative and antispasmodic action, including mixing phenobarbital, ethyl ester of α-bromisovalerianic acid, peppermint oil with excipients, according to the invention, phenobarbital is first mixed with excipient, the mixture is prepared separately α-bromisovalerianic acid ethyl ester and peppermint oil, the mixture of essential oils being less than 4.5% of the weight of the tablet, tablet i g of the content of the capsule, add microcrystalline cellulose, powders with a developed surface of the crystals, excipients, disintegrants and glidants, the resulting mixture is added to a mixture of phenobarbital with filler and tablets are pressed, and then they are coated with a coating containing β-cyclodextrin in a dose of up to 10 % dry coating weight.

As fillers, lactose, starch, glycine, calcium diphosphate, calcium dihydrogen phosphate, glucose, sorbitol and / or mixtures thereof can be used.

As baking powder can use starch and its derivatives: crospovidone, croscarmellose and / or mixtures thereof.

Magnesium stearate, sodium fumarate, talc, polyvinylpyrrolidone and / or mixtures thereof can be used as glidants.

In the process of coating, the tablets are heated and treated with heated air.

As the shell, a film, a sugar coating or combinations thereof can be used.

A film is made by mixing a film forming agent and a 1% β-cyclodextrin solution.

The sugar shell is made by mixing sugar, magnesium carbonate, aerosil, polyvinylpyrrolidone, titanium dioxide, talc and a solution of β-cyclodextrin or other components used in the industry for coating tablets.

Microcrystalline cellulose used in the composition of the solid dosage form has a multifunctional role. It, being a substance with a developed surface of particles and a low specific density, promotes sorption and transfer of liquid substances to a solid state. Due to its plasticity, it acts as a filler, providing mechanical strength of the tablet. When the tablet comes in contact with water, microcrystalline cellulose due to swelling can improve disintegration. If the last two properties are described in the literature (Handbook of Pharmaceutical Excipients Ed. I. Rowe et all. 5 Ed, Washington, 2006), then the first property is inherent in microcrystalline cellulose in this drug.

As excipients, experimentally tested substances are given, the use of other substances approved for use as excipients by Pharmacopoeias or other legislative documents is obvious to a qualified specialist, but their quantity, effectiveness and role in this drug can only be established after experimental verification.

Cyclodextrins are pharmacologically inert products of the enzymatic transformation of starch and have a cavity in the molecule, which may include medicinal substances. Correspondence of the size of the cavity in the cyclodextrin molecule and the size of the drug substance makes it possible to interact.

Improving the stability of the coating is achieved by introducing a solution of β-cyclodextrin in a dose of up to 10% of the weight of the dry coating. An increase in the amount of β-cyclodextrin is impossible, because the shell loses its elasticity and adhesiveness to the tablet surface. When the vapor of volatile substances is absorbed by cyclodextrins, the quality of the shell does not change both for thin film shells and for coated tablets.

The selection of components and their quantitative composition, stages, modes and parameters of the technological cycle makes it possible to obtain a sedative and antispasmodic drug in the form of tablets or capsules, which ensures dosage accuracy and the inability to overdose due to inexperience and carelessness of patients or in critical situations, the convenience of using the drug on the road .

The invention is illustrated by examples.

Example 1

Phenobarbital is mixed with calcium diphosphate, a mixture of ethyl ester of α-bromisovalerianic acid and peppermint oil, microcrystalline cellulose, aerosil, starch, polyvinylpyrrolidone, pectin, calcium alginate, magnesium stearate, and talc are pressed and 200 mg tablets are pressed. The tablets were film coated using a 1% aqueous solution of β-cyclodextrin.

The composition per tablet is shown in table 1.

Table 1 Component Wt% Phenobarbital 3.75 Α-bromisovalerianic acid ethyl ester 4.1 Peppermint Oil 0.29 Calcium Diphosphate 53.36 Pectin 5,0 Calcium alginate 10.0 Microcrystalline cellulose 8.5 Aerosil 3.38 Starch 6.27 Talc 1.45 Polyvinylpyrrolidone 2.9 Magnesium stearate one

Due to the fact that calcium diphosphate has a significant specific gravity and requires considerable pressure for pressing, in order to reduce these indicators and achieve optimal compression of the tablet mass, it is necessary to increase the amount of microcrystalline cellulose, which also provides a more efficient pore system in tablets and thus contributes to greater effectiveness of the loosening properties of starch.

The shell contains 0.3 mg of β-cyclodextrin.

Example 2

Α-bromisovalerianic acid ethyl ester is mixed in a mixer with peppermint oil, the resulting mixture is added to moistened cyclodextrin and mixed for 1-2 minutes, dried and granulated, after which the granulate is mixed with powders of phenobarbital, glucose, starch, microcrystalline cellulose, lactose, magnesium stearate . The resulting mixture was tabletted with an average weight of 140 mg.

Table 2 shows the ratio of the components of the claimed composition.

table 2 Component Wt% Α-bromisovalerianic acid ethyl ester 5.86 Phenobarbital 5.36 Peppermint Oil 0.40 β-cyclodextrin 39.68 Starch 9.3 Lactose 31.28 Microcrystalline cellulose 7.5 Magnesium stearate 0.64

The shell contains 0.3 mg of β-cyclodextrin.

Example 3

The inventive composition is obtained analogously to example 1. The composition per tablet is shown in table 3.

Table 3 Component Wt% Phenobarbital 3.75 Α-bromisovalerianic acid ethyl ester 4.1 Peppermint Oil 0.29 Hop oil 0.04 Calcium Diphosphate 53.32 Pectin 5,0 Calcium alginate 10.0 Microcrystalline cellulose 13.5 Aerosil 3.38 Starch 6.27 Talc 1.45 Polyvinylpyrrolidone 2.9 Magnesium stearate one

The shell contains 0.3 mg of β-cyclodextrin.

Example 4

Α-bromisovalerianic acid ethyl ester is mixed in a mixer with peppermint oil, the resulting mixture is added to moistened cyclodextrin and mixed for 20-30 minutes to increase the mass density, the mass is unloaded, dried and granulated, after which the granulate is mixed with phenobarbital, glucose, starch, microcrystalline cellulose, lactose, magnesium stearate. The resulting mixture was tabletted with an average tablet weight of 100 mg.

The inventive composition is obtained analogously to example 2.

The composition per tablet is shown in table 4.

Table 4 Component Wt% Phenobarbital 9.35 Α-bromisovalerianic acid ethyl ester 10.25 Peppermint Oil 0.73 Lactose 2,37 Microcrystalline cellulose 2 β-cyclodextrin 70 Starch 5.00 Magnesium stearate 0.3

The shell contains 0.3 mg of β-cyclodextrin.

Example 5

Α-bromisovalerianic acid ethyl ester is mixed in a mixer with peppermint oil, hop oil, the resulting mixture is added to moistened cyclodextrin and mixed for 20-30 minutes to increase the mass density, the mass is unloaded, dried and granulated, after which the granulate is mixed with phenobarbital powders glucose, starch, microcrystalline cellulose, lactose, magnesium stearate. The resulting mixture was tabletted with an average tablet weight of 100 mg.

The inventive composition is obtained analogously to example 2.

The composition per tablet is shown in table 5.

Table 5 Component Wt% Phenobarbital 9.35 Α-bromisovalerianic acid ethyl ester 10.25 Peppermint Oil 0.73 Hop oil 0.1074 Lactose 2,37 Microcrystalline cellulose 2 β-cyclodextrin 70 Starch 2.2626 Magnesium stearate 0.3

Example 6

Α-bromisovalerianic acid ethyl ester is mixed in a mixer with peppermint oil, the resulting mixture is added to moistened cyclodextrin and mixed for 1-2 minutes, dried and granulated, after which the granulate is mixed with powders of phenobarbital, glucose, starch, microcrystalline cellulose, lactose, magnesium stearate . The resulting mixture was tabletted with an average weight of 140 mg.

Table 6 shows the ratio of the components of the claimed composition.

Table 6 Component Wt% Α-bromisovalerianic acid ethyl ester 5.86 Phenobarbital 5.36 Peppermint Oil 0.40 β-cyclodextrin 39.68 Starch 9.3 Lactose 24.28 Glucose 7.0 Microcrystalline cellulose 7.5 Magnesium stearate 0.64

The shell contains 0.3 mg of β-cyclodextrin.

Example 7

Phenobarbital is mixed with lactose, a mixture of ethyl ester of α-bromisovalerianic acid and peppermint oil, microcrystalline cellulose, aerosil, starch, talc, polyvinylpyrrolidone, calcium alginate, magnesium stearate are added and tablets with an average weight of 200 mg are pressed. The resulting tablets are sugar coated. Coating weight 200 mg.

The composition per tablet is shown in table 7.

Table 7 Component Wt% Phenobarbital 3.75 Α-bromisovalerianic acid ethyl ester 4.1 Peppermint Oil 0.3 Lactose 17.35 Microcrystalline cellulose 6.5 Aerosil 3.0 Starch 4.0 Talc 1,5 Polyvinylpyrrolidone 1,0 Calcium alginate 8.0 Magnesium stearate 0.5

Shell, mg:

sugar 36.6 magnesium carbonate 7.5 polyvinylpyrrolidone 0.67 aerosil 0.5 talc 0.5 titanium dioxide 1,0 β-cyclodextrin 0.62.

Example 8

Phenobarbital is mixed with lactose, a mixture of ethyl ester of α-bromisovalerianic acid, peppermint oil and hop oil is added. Microcrystalline cellulose, aerosil, starch, talc, polyvinylpyrrolidone, calcium alginate, magnesium stearate are added and tablets with an average weight of 200 mg are pressed. The resulting tablets are sugar coated. Coating weight 200 mg.

The composition per tablet is shown in table 8.

Table 8 Component Wt% Phenobarbital 3.75 Α-bromisovalerianic acid ethyl ester 4.1 Peppermint Oil 0.3 Hop oil 0,045 Lactose 17.35 Microcrystalline cellulose 6.5 Aerosil 3.0 Starch 4.0 Talc 1,5 Polyvinylpyrrolidone 1,0 Calcium alginate 8.0 Magnesium stearate 0.5

Shell, mg:

sugar 36.6 magnesium carbonate 7.5 polyvinylpyrrolidone 0.67 aerosil 0.5 talc 0.5 titanium dioxide 1,0 β-cyclodextrin 0.6.

The data presented indicate the multifunctional action of the excipient system, which ensures the optimality of the physicomechanical properties of the solid dosage form.

Table 9 shows the data on the time of formation of the complex with β-cyclodextrin.

Table 9 Complex formation time Example 2 1 min 20 s Example 5 30 minutes Example 6 1 min

Table 10 shows the data on the physicomechanical properties of the obtained tablets.

Table 10 The mass of the tablet core, mg Strength, N Disintegration, min Abrasion,% Dissolution of phenobarbital,% Example 1 200 70 8 0.05 75 Example 2 140 70 5 0.01 85 Example 3 200 85 9 0.05 80 Example 4 one hundred 80 5 0,03 85 Example 5 one hundred 85 5 0,03 85 Example 6 one hundred 68 5 0,03 80 Example 7 200 70 8 0.05 75 Example 8 200 70 8 0.05 75

The advantages of the solid dosage form obtained according to the claimed invention, compared with the prototype are shown in table 11.

Table 11 Indicators According to the invention According to the prototype Benefits Dose of the drug 1 tablet 20 drops Usability The need for dilution with water Absent Necessary Dosing accuracy Average weight deviation ± 2% 7 to 20%, depending on packaging Dosing accuracy The deviation of the average weight from the number of drugs in the package Absent ± 16% Dosing accuracy Compliance with the average weight of documentation ± 2% + 30%; Dosing accuracy -3%

Thus, the claimed invention fulfills the task of creating tablets of a combined preparation of sedative and antispasmodic action, which according to the kinetics of antispasmodic action correspond to the dosage form - drops and have an advantage over it in the accuracy and affordability of the dosage.

Claims (20)

1. A drug of sedative and antispasmodic action, containing ethyl ester of α-bromisovalerianic acid, phenobarbital and peppermint oil, characterized in that it additionally contains microcrystalline cellulose, auxiliary substances for creating a solid dosage form in the form of tablets in the following ratio, wt.% :
Α-bromisovalerianic acid ethyl ester 1.37-8.2 Phenobarbital 1.25-7.5 Peppermint Oil 0.16-0.58 Microcrystalline cellulose 2-15 Excipients rest
moreover, the tablets are coated, which includes β-cyclodextrin in a dose of up to 10% of the weight of the dry coating. 2. The drug according to claim 1, characterized in that as an auxiliary substance additionally contains β-cyclodextrin in a dose of up to 70 wt.%. 3. The drug according to claim 1, characterized in that it further comprises hop oil in a dose of 0.0229-0.09 wt.%. 4. A method of manufacturing a medicinal product of sedative and antispasmodic action, comprising mixing phenobarbital, ethyl ester of α-bromisovalerianic acid, peppermint oil with auxiliary substances, characterized in that the ethyl ester of α-bromosovalerianic acid is first mixed with peppermint oil, the amount of the mixture being more than 4.5% of the total weight of the tablet, core tablet or capsule content, the mixture is added to moistened β-cyclodextrin, the amount of which is up to 70% by weight the mass of the tablet core is mixed for 1-2 minutes, the resulting mixture is dried, granulated, after which the granulate is mixed with powders of phenobarbital, microcrystalline cellulose, excipients, disintegrants and glidants, the tablets are pressed, and then they are coated with a shell containing β-cyclodextrin in a dose of up to 10% of the weight of the dry coating. 5. The method according to claim 4, characterized in that the hop oil is additionally added. 6. The method according to claim 4 or 5, characterized in that during the coating process, the tablets are heated and treated with heated air. 7. The method according to claim 4 or 5, characterized in that the fillers used are lactose, starch, glycine, calcium diphosphate, calcium dihydrogen phosphate, glucose, sorbitol and / or mixtures thereof. 8. The method according to claim 4 or 5, characterized in that the starch and its derivatives are used as baking powder: crospovidone, croscarmellose and / or mixtures thereof. 9. The method according to claim 4 or 5, characterized in that the use of magnesium stearate, sodium fumarate, talc, polyvinylpyrrolidone and / or mixtures thereof as sliding substances. 10. The method according to claim 4 or 5, characterized in that the film, sugar coating or combinations thereof are used as a coating. 11. The method according to claim 10, characterized in that the film is made by mixing the substance forming the film and a 1% solution of β-cyclodextrin. 12. The method according to claim 10, characterized in that the sugar shell is made by mixing sugar, magnesium carbonate, aerosil, polyvinylpyrrolidone, titanium dioxide, talc and a solution of β-cyclodextrin or their derivatives or other components used in the industry for coating tablets. 13. A method of manufacturing a sedative and antispasmodic drug, including mixing phenobarbital, ethyl ester of α-bromisovalerianic acid, peppermint oil with excipients, characterized in that the phenobarbital is first mixed with excipient, an α-bromisovalerianic ethyl ester mixture is prepared separately peppermint acids and oils, the mixture of essential oils being less than 4.5% of the weight of the tablet, core tablet or capsule content, add micro ristallicheskuyu cellulose powders with a developed surface crystals, adjuvants, disintegrants and lubricants, the resulting mixture was added to a mixture of phenobarbital with filler and compressed into tablets, then they are coated with a shell containing β-cyclodextrin at a dose of up to 10% by weight of the dry coating. 14. The method according to item 13, wherein the fillers are lactose, starch, glycine, calcium diphosphate, calcium dihydrogen phosphate, glucose, sorbitol and / or mixtures thereof. 15. The method according to item 13, wherein the starch and its derivatives are used as baking powder: crospovidone, croscarmellose and / or mixtures thereof. 16. The method according to p. 23, characterized in that as the moving substances use magnesium stearate, sodium fumarate, talc, polyvinylpyrrolidone and / or mixtures thereof. 17. The method according to p. 13, characterized in that during the coating process, the tablets are heated and treated with heated air. 18. The method according to item 13, wherein the film, the sugar coating, or combinations thereof are used as a coating. 19. The method according to p. 18, characterized in that the film is made by mixing the substance forming the film, and a 1% solution of β-cyclodextrin. 20. The method according to p. 18, characterized in that the sugar shell is made by mixing sugar, magnesium carbonate, aerosil, polyvinylpyrrolidone, titanium dioxide, talc and a solution of β-cyclodextrin or other components used in the industry for coating tablets.