Pharmaceutical composition having properties cardioselektivee1-blocker

 

(57) Abstract:

The invention relates to chemical-pharmaceutical industry, namely to the drug, possessing properties cardioselektivee 1-blocker. The invention lies in the fact that the proposed structure includes atenolol, magnesium carbonate, Aerosil, microcrystalline cellulose, starch, calcium stearate, talc, sodium lauryl sulphate, hydroxypropylcellulose. The invention provides for obtaining a pharmaceutical composition which conforms to pharmacopoeial requirements and stable during storage.

The invention relates to chemical-pharmaceutical industry, namely the creation of a drug that has the properties cardioselektivee 1-blocker.

-blockers are a group of drugs that have specific blocking effect on the effects associated with stimulation-adrenoreaktivnyh systems. Contacting-adrenergic receptors, they have in connection with the peculiarities of their structure and physico-chemical properties are not stimulating and blocking (antagonist) the action preventing action on the adrenergic receptors of neurotransmitter-norepinephrine. They are widely used for treatment is Ramiah.

Various-blockers differ in their selectivity of action on 1 - and 2-adrenergic receptors. Drugs that selectively block 1-adrenergic receptors, as cardioselektivei (atenolol, metoprolol, talinolol). Other (propranolol, inderal, oxprenolol, timolol and others) operate simultaneously on 1-adrenergic receptors (heart) and 2-adrenoreceptor (bronchi, blood vessels), and they are called non-selective (non-selective). It is believed that in the acute period of myocardial infarction cardioselektivee 1-blockers are more secure than non-selective drugs, as they do not increase the total peripheral resistance.

One of the representatives cardioselektivee 1-adrenoblokatorov is atenolol. In connection with the electoral action of atenolol is well tolerated and can be given to patients with a tendency to bronchospasm and spasm of peripheral vessels with less risk than non-selective blockers. The purpose of atenolol (first intravenously and then orally) immediately after the onset of myocardial infarction resulted in studies to reduce mortality by reducing cases of a broken heart and primary ventricular fibrillation (Mashkovsky M. D. Medicines. The mos is intended to pelletizing. Therefore, to create stable for quite a long time meet pharmacopoeial requirements of the dosage form is necessary to introduce auxiliary substances in quantities defined pharmaceutical and therapeutic usefulness. The process of obtaining tablets of atenolol has some specific characteristics, due to the low compressibility of the substance. For achieving high hardness of the tablets is not always possible to achieve the desired disintegration and dissolution of tablets. Conversely, if a satisfactory dissolution of the drug insufficient hardness of tablets, pills break and crumble at the stage of production and distribution. In addition, in the production of the coating substance on the walls of the process equipment. Thus, there is a strong need for selection of the optimal ratio of the main and auxiliary substances.

In European patent (EP 0598309, INVERNI DELLA BEFFA SPA. 25.05.94) presents a multilayer system with controlled release of atenolol. It is a mixture of pellets of different composition. Some of the granules has a composition, wt.%:

Atenolol - 24

Acetylcellulose - 2

Talk

A method of producing granules provides a wet granulation; moisturizing agent is a solution of acetamidoacrylate (acetamidoacrylate dissolved in 560 ml of a mixture containing ethanol and acetone in the ratio 1:2).

Another type of granules has the following composition, wt.%:

Lactose - 88

Hydroxyethylcellulose - 2,5

Talc - 7,5

Magnesium stearate - 2

The next type of granules has a composition, wt.%:

Lactose - 88

Magnesium stearate - 1

Talc - 11

To obtain a finished dosage forms mix different types of granules in equal mass ratio and tabletirujut.

The disadvantages of the proposed structure should be attributed to the high content of talc in the composition, which exceeds the prescribed State Pharmacopia XI limit 3 wt.% (The state Pharmacopoeia of the USSR XI, editions 1, 2, Moscow, 1998). In addition, obtaining a multilayer dosage forms, as a rule, it is technologically difficult.

Closest to the proposed invention is the preparation disclosed in patent EP 0454396, SQUIBB and SONS INC, 30.10.91. The drug is made in the form of tablets and has the following composition, wt.%:

Atenolol - 28

Citric acid - 1,5

Microcrystallites the pharmaceutical compositions include high content of microcrystalline cellulose (68,5%). Currently, standard pharmaceuticals as a filler and a binder is applied microcrystalline cellulose. However, made on the basis of microcrystalline cellulose tablets along with high raspadaemost are characterized by a very short period of existence (Pharmazeutische Technologie, Edited by H. Sucker, Stuttgart, 1978, S. 373) that adversely affects the quality of pills in their possession.

The objective of the invention is to develop a pharmaceutical composition having properties cardioselektivee 1-blocker. which meets all pharmacopoeial requirements and stable during storage.

This object is achieved in that a pharmaceutical composition in the form of tablets, having the properties cardioselektivee 1-blocker containing atenolol and excipients, characterized in that as auxiliary substances it contains magnesium carbonate, Aerosil, microcrystalline cellulose, starch, calcium stearate, talc, sodium lauryl sulphate, hydroxypropylcellulose in the following ratio, wt.%:

Atenolol - 22,1-28,3

Magnesium carbonate - 10,5-30,5

Aerosil - 0,4 1-3

Sodium dodecyl sulfate - 0,5-2

Hydroxypropylcellulose - 0,8-1,8

Specially selected combination of components provides sufficient hardness of the resulting tablets and high raspadaemost. Introduction moving and apadravya substances in the composition (calcium stearate, Aerosil, talc) significantly reduces the sticking of tablet mass during pelletizing and thereby improves the manufacturability of the process. Introduction starch having anti-friction properties can reduce the content of other anti-friction additive is talc to the value not exceeding the allowed Pharmacopoeia GF XI (3 wt.%). The combination of all excipients provides a high rate of dissolution, in which the optimal release profile of the active substance: 45 minutes released at least 75% of the atenolol.

The obtained pharmaceutical composition complies with the requirements of the State Pharmacopoeia XI, stable during prolonged storage (shelf life 2 years).

The invention is illustrated by the following examples.

Example 1.

An example of a composition having properties cardioselektivee 1-blocker, wt.%:.

A method of obtaining a composition having properties cardioselektivee 1-blocker.

1. Preparation of raw material

The starch is dried. The calcined talc. Aerosil, atenolol, dry starch, calcium stearate, calcined talc, magnesium carbonate, microcrystalline cellulose sift.

2. Preparation of 2% aqueous-alcoholic solution hydroxypropylcellulose (klucel).

In the reactor pour purified water, heated and with stirring, add Cluzel, stand under stirring for 5-10 minutes, then cooled and passed to the stage of preparation of the wet granulate.

3. Getting wet granulate.

In the mixer load magnesium carbonate basic sifted, atenolol sifted, microcrystalline cellulose were sifted, starch sifted. Mixer tight-fitting lid, turn the mixer and the mixture is stirred for 10 minutes Then moisturize with stirring a 2% solution of klucel, stir for 3-5 minutes until evenly moistened mass.

The wet mixture of podaxis granulator, after which the mixture is discharged into the container or spread out on trays layer (1.5 to 2.0) cm and is passed to the drying operation.

4. Drying and dry granulation.

The wet granulate is dried in the dryer for 3-4 hours at a temperature of (555)oC. the Dry granules are poured into a container and sent for dry granulation. On the granulator dry granules are forced through the mesh and collected in the tank.

The dry granulate is passed through the receiving tablemats and tableting.

5. Preparation of tablet mass.

The dry granulate is loaded into the drageeing boiler for dusting, add calcium stearate, Aerosil, talc, sodium lauryl sulphate, ground in the granulator substandard tablets and screenings, all mixed for 5-10 minutes until smooth and pass through tableting.

6. Tableting and rejection.

Tableting is performed on a rotary press. Tablets Atenolol should have a face shape, solid edge, smooth and uniform surface.

Tablets should possess sufficient strength mechanical influences.

Rejected substandard tablets, gather them in almacenista composition in the form of tablets, having the properties cardioselektivee 1-blocker containing atenolol and excipients, characterized in that as auxiliary substances it contains magnesium carbonate, Aerosil, microcrystalline cellulose, starch, calcium stearate, talc, sodium lauryl sulphate, hydroxypropylcellulose in the following ratio, wt.%:

Atenolol - 22,1-28,3

Magnesium carbonate - 10,5-30,5

Aerosil - 0,4-1,1

Microcrystalline cellulose - 15,2-25,5

Starch - 20,4 of 40.8

Calcium stearate - 0,5-1,9

Talc - 1-3

Sodium dodecyl sulfate - - 0,5-2

Hydroxypropylcellulose - 0,8-1,8 b

 

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