RU2384336C1 - Pharmaceutical composition for correction of psychosomatic manifestations - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: pharmaceutical composition contains alimemazine as an active component, and target adjuvants: lactose, potato starch, microcrystalline cellulose, kollidon, magnesium stearate in the following ratio. The composition is made in the form of coated tablets with the coating containing polyvinyl alcohol, talc, polyethylene glycol, titanium dioxide, acceptable dying agents.

EFFECT: pharmaceutical composition extends range of medical products, meets all of the standard requirements and has shelf-life of 2 years.

5 cl, 2 ex

Description

The invention relates to the field of pharmacology and medicine, namely to pharmaceutical formulations for the correction of psychosomatic manifestations of various etiologies.

The growing prevalence of psychosomatic disorders has become an everyday reality, and according to various sources, the number of patients requiring treatment by a psychiatrist is 30-50% (Drobizhev M.Yu. Psychopharmacotherapy in the somatic network // Psychiatry and psychopharmacotherapy. - Volume 2. - No. 2. - 2000. - 4 p.).

When treating patients with psychosomatic disorders with psychopharmacotherapeutic agents, it is advisable to use one drug that should have a minimal number of side effects, not interact with somatotropic drugs, be easy to use and safe in case of overdose. These conditions are satisfied with tranquilizers, which are most often prescribed, as well as some antidepressants and antipsychotics.

The pharmacological action of tranquilizers is addressed mainly to anxiety conditions. The most significant limitation to the use of these drugs is the high risk of drug dependence during long-term treatment, because insufficient duration of therapy leads to the resumption of symptoms. In addition, the achievement of an effective dosage is often accompanied by side effects in the form of psychomotor inhibition. Modern antidepressants are devoid of these shortcomings, but the therapeutic target for them are disorders with a depressive component or obsessions. The above requirements for psychotropic drugs for the treatment of psychosomatic disorders meet antipsychotics and are "first choice" drugs. This list includes individual derivatives of phenothiazine (alimemazine, thioridazine, perphenazine), thioxanthene (chlorprothixene), benzamides (sulpiride, thiapride) (Consilium Medicum No. 2/1999).

The absence of significant extrapyramidal side effects, behavioral toxicity, weak anticholinergic effect, and special “softness” of action gave grounds to designate these drugs as “small” antipsychotics and led to the widespread use of these drugs for the treatment of “borderline” mental disorders (Avrutsky G.Ya., Neduva A .A. Treatment of the Mentally Ill. A Guide for Doctors. - 2nd ed., Revised and revised - M .: Medicine. 1988. - 528 p.). In small doses, they eliminate irritability, anxiety and have some activating effect up to a mild antidepressant. As the dosage increases, their sedative and antipsychotic effects increase. In addition to symptomatic psychoses, alcoholism, this group of drugs is effective in a wide range of other psychosomatic disorders. For example, all drugs of this group are characterized to one degree or another by antiemetic, analgesic and hypnotic action. There are individual characteristics of each drug (Drobizhev M.Yu. Cardiological aspects of the tolerance and safety of antipsychotics. // Psychiatry and psychopharmacotherapy. - Volume 6. - No. 2. - 2004. - 13 pp.). For example, sulpiride reduces gastric secretion, unlike other drugs that have a mild hypotensive effect, it slightly increases blood pressure. Chlorprotixen promotes the excretion of uric acid in the urine and is therefore especially indicated for patients with gout. Thiapride has a pronounced analgesic effect, and thioridazine is especially effective in relieving cardialgia. Alimemazine is characterized by good absorption in various routes of administration, has minimal side effects, has a short half-life in the body.

The high safety of the drugs under discussion makes it possible to prescribe them for the treatment of psychosomatic disorders in a wide range of doses with different multiples during the day for both elderly and children, and to achieve the best result with minimal side effects.

It is known (Medicines. Handbook edited by M.A. Klyuyev, 2001) that alimemazine is released in the form of tablets, drops, and injection solution under the trade name "Teralen". Closest to the proposed invention is a dosage form in the form of a tablet containing an effective amount of alimemazine and additional substances: lactose monohydrate, wheat starch, silicon, erythrosine, silica anhydride, aerosil, magnesium stearate, zein, diethyl phthalate, butyl acetoricinolate, acetate erythrosine.

The aim of this invention is to expand the arsenal of drugs with a psychosomatic effect, using a pharmaceutical composition, which is based on alimemazine. At the same time, the resulting composition must comply with the requirements of the current Gosfarmakopeya XI edition, be more economical, stable during storage and quickly release the active substance in the gastrointestinal tract.

The goal is achieved by a pharmaceutical composition with a psychosomatic effect, including alimemazine tartrate and target excipients as an active component.

As target additives, lactose, potato starch, microcrystalline cellulose, collidone, magnesium stearate are used in the following ratio of components, wt.%:

Alimemazine tartrate 3.0-7.0 Lactose 48.0-51.0 Potato starch 15.0-16.0 Microcrystalline cellulose 24.0-25.0 Collidon 3.0-4.3 Magnesium stearate 0.8-1.2

When creating a solid dosage form in the form of tablets of the claimed medicinal product to give the best technological properties, namely flowability and compressibility of the active substance, potato starch in the amount of 15.0-16.0 wt.% Was used as a filler.

To ensure the strength of the tablets, microcrystalline cellulose was used as a binder, which is relatively inexpensive and has a wide range of molecular weights, effectively controls the release rate of drugs, which helps to maintain a therapeutically active concentration of the drug substance in the body for a long time, including the flow of drug substance with set speed.

In order to increase the fluidity of the tableted masses, to prevent them from sticking to the punches and the walls of the holes of the matrix, magnesium stearate and collidone were used as lubricants and sliding substances. They provide good flowability and uniform supply of tableted masses from the hopper into the matrix, which guarantees the accuracy and consistency of the dosage of the drug substance. Contribute to the easier ejection of tablets from the matrix, preventing the formation of scratches on their faces. The amount of glidants is 0.8–1.2 and 3.0–4.3 wt%, respectively.

To give acceptable organoleptic properties, the composition of the composition introduced lactose in an amount of from 48.0 to 51.0 wt.%, Which makes it possible to improve the taste of the drug, sweeten the taste of the active substance alimemazine tartrate.

The proposed combination of active principle and excipients is determined experimentally and is optimal. The result is a mixture of substances with good technological properties in the process of granulation and tabletting, and the resulting tablets have properties that satisfy the requirements for a pharmaceutical agent, i.e. they have a marketable appearance without chips and cracks, have sufficient strength and disintegration, are stored for at least 2 years, while providing a high clinical effect, convenient dosage and high bioavailability of incoming components.

The new pharmaceutical composition is in the form of a solid coated dosage form, preferably in the form of a tablet. The presence of the shell of the claimed composition gives, firstly, the stability of the composition during storage, and secondly, improves its appearance and organoleptic properties.

As a shell, a composition based on polyvinyl alcohol, talc, polyethylene glycol, titanium dioxide, acceptable dyes or the Opadry II brand ready mix is proposed.

The most common ways to obtain tablets are three technological schemes: with wet granulation, dry granulation and direct compression (Technology of dosage forms / Edited by Ivanova L.A. - M .: Medicine, 1991, v.2, p.142).

The possibility of carrying out the invention is illustrated by the following examples, but is not limited to.

Example 1

The manufacturing process of tablet cores is carried out by wet granulation.

Alimemazine tartrate, lactose, potato starch and magnesium stearate are sieved through a sieve.

Distilled water heated to a temperature of 30-40 ° C is charged into a container, and collidone is added with constant stirring. Mixing lead to complete dissolution of the dry matter. The solution was cooled to room temperature, filtered through a sieve, and transferred to the wet granulate production step.

Lactose 12.11 kg (50.46%), potato starch 3.84 kg (16%), microcrystalline cellulose 6.00 kg (25%) and alimemazine tartrate 0.788 kg (3.28%) are mixed for 5 minutes. Moisturize with a 7% aqueous solution of collidone in an amount of 0.48 kg (4.26%). Stir until the moisture is evenly distributed. A humidified mass of 30.928 kg is discharged from the mixer, laid out on trays and dried in an oven at a temperature of 40 ° C to a residual moisture content of 3.5-4.5%. The dried granulate is discharged from the dryer, cooled to room temperature and passed through a granulator with a hole diameter of 1.5 mm. The granulate is passed to the stage of preparation of the tablet mass.

Dry granulate is loaded into the mixer, 0.24 kg (1%) magnesium stearate is added and mixed for 1-2 minutes. The powdered mass is discharged from the mixer and transferred to the tableting step.

Tableting is carried out on a rotary press, using round punches with a risk, biconvex. The weight of the tablet cores is 0.16 g (0.148 g to 0.172 g).

In the process of tabletting, the appearance and fracture strength of the tablet cores are controlled. The breaking strength of tablet cores is from 60-70 N. The tablet cores are white or almost white, biconvex, with solid edges, a smooth and uniform surface, without cracks and chips.

The obtained tablet core is dedusted, kept at room temperature in a closed container for 10-12 hours, in a dark place. The abrasion resistance of the tablet cores is at least 99.8%.

The obtained core tablets are passed to the film coating step.

To coat the tablets, the core cores are placed in a chamber with a spray device and, when the drum is rotated, a film-forming composition is continuously applied to the tablets, for which an aqueous suspension of Opadray II powder with a mass concentration of 19 ± 1% is prepared. The film coating on the tablet cores is carried out after they are heated to 38-42 ° C, with constant stirring and simultaneous drying with warm air, after which they are unloaded in a plastic container and kept for 6-8 hours at room temperature.

The resulting tablets meet all the requirements of the State Pharmacopoeia XI ed. and have a shelf life of 2 years. After 45 minutes, at least 70% (Q) of alimemazine tartrate passes into the solution.

Example 2

The production process of tablet cores is carried out according to example 1, with the following ratios of ingredients: lactose 11.505 kg (49.17%), potato starch 3.64 kg (15.56%), microcrystalline cellulose 5.72 (24.44%), alimemazine tartrate 1.365 kg (5.83%), 0.47 kg collidone (4%) and magnesium stearate 0.23 kg (1%). The mass of tablet cores is 0.18 g ± 7.5% (from 0.167 g to 0.193 g).

In the process of tabletting, the appearance and fracture strength of the tablet cores are controlled. The breaking strength of tablet cores is from 60-70 N. The tablet cores are white or almost white, biconvex, with solid edges, a smooth and uniform surface, without cracks and chips.

The obtained tablet core is dedusted, kept at room temperature in a closed container for 10-12 hours, in a dark place. The abrasion resistance of the tablet cores is at least 99.8%.

The obtained core tablets are passed to the film coating step. The film-coating is carried out according to example 1.

The resulting tablets meet all the requirements of the State Pharmacopoeia XI ed. and have a shelf life of 2 years. After 45 minutes, at least 70% (Q) of alimemazine tartrate passes into the solution.

Claims (5)

1. The pharmaceutical composition for the correction of psychosomatic disorders, comprising as an active component alimemazine tartrate and target excipients, characterized in that it contains an effective amount of alimemazine tartarate and as target additives it contains lactose, potato starch, microcrystalline cellulose, collidone, magnesium stearate in the following ratio of ingredients, wt.%:
Alimemazine tartrate 3.0-7.0 Lactose 48.0-51.0 Potato starch 15.0-16.0 Microcrystalline cellulose 24.0-25.0 Collidon 3.0-4.3 Magnesium stearate 0.8-1.2 2. The pharmaceutical composition according to claim 1, characterized in that it is made in the form of a solid dosage form. 3. The pharmaceutical composition according to claim 2, characterized in that it is made in the form of coated tablets. 4. The pharmaceutical composition according to claim 3, characterized in that the shell is up to 5% by weight of a tablet without a shell. 5. The pharmaceutical composition according to claim 4, characterized in that the shell contains polyvinyl alcohol, talc, polyethylene glycol, titanium dioxide, acceptable colorants or the finished mixture of the brand "Opadry II".