Medicinal formulation eliciting anti-anginal effect and method for its preparing

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a medicinal formulation consisting of a core and the stomach-dissolving envelope. The core comprises trimetazidine dihydrochloride as an active component, and starch, mannitol, povidone, magnesium stearate, croscarmelose and microcrystalline cellulose as accessory substances. The envelope comprises hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, magnesium stearate and acid red as a dye. Also, invention describes a method for making the trimetazidine medicinal formulation. Trimetazidine tablets show high mechanical strength in the low pressing strength (3.5-5 kH). The composition of the medicinal formulation provides releasing 80% of trimetazidine for 30 min.

EFFECT: improved and valuable properties of formulation.

3 cl, 1 tbl, 1 ex

 

The invention relates to medicine, in particular to the pharmacy, and can be used in the manufacture of solid dosage forms of drugs that have antianginal effect and can be used for long-term therapy of coronary artery disease: prevention of angina attacks (monotherapy or combination therapy); treatment of cochleo-vestibular disorders of ischemic nature (such as dizziness, tinnitus, hearing loss); chorioretinal vascular disorders with ischemic component.

The closest to the invention is a pharmaceutical form having antianginal action, which is a tablet consisting of a core and shell and containing as active substance kernel derivative of piperazine and excipients: starch, lactose, calcium calcium stearate.

The way to obtain this form involves mixing active with AIDS, subsequent hydration water mixture and granulating the obtained hydrated mixture. Then the granulate is dried, optivault the calcium stearate and tabletirujut (U.S. patent No. 4370329, publ. 25.01.1983).

Object of the invention is the creation of a domestic drug that has high bioavailability with high mechanical strength.

The technical is the ski of the invention is to accelerate raspadaemosti tablets and release Trimetazidine, to provide high strength tablets at low pressing force, as well as providing the minimum of the dispersion of tablets by weight, the strength and speed of dissolution of Trimetazidine.

The problem is solved dosage form having antianginal action, consisting of a nucleus containing as active Trimetazidine the dihydrochloride and excipients, and dissolving in the stomach membrane, and the nucleus contains as excipients starch, mannitol, povidone, magnesium stearinovokisly, croscarmelose and microcrystalline cellulose, in the following components in wt.%:

Trimetazidine a dihydrochloride5,0-42,0
Corn starch16,0-29,0
Mannitol12,0-of 17.0
Povidone5,0-9,5
Magnesium stearinovokisly0.5 to 1.5
Crosscarmellose1,5-5,0
Microcrystalline cellulose23,0-33,0,

and the shell contains the following components in wt.%:

Oksipropilmetiltselljuloza57,0-82,0
The polyethylene glycol 5,0-10,0
Titanium dioxide10,0-25,0
Magnesium stearinovokisly1,0-3,0
Dye acid red2,0-5,0

In private embodiments of the invention, the problem is solved in that form as starch contains corn starch.

The technical result is also achieved by a method of manufacturing a dosage form, in accordance with which is mixed Trimetazidine the dihydrochloride, mannitol, starch and microcrystalline cellulose, the resulting mixture is moistened with a solution of povidone, re-mix, damp granulation, subsequent drying, dry granulation, the powder mixture croscarmellose and magnesium stearinovokisly followed by pelletizing and coating shell of an aqueous suspension containing oksipropilmetiltselljuloza, polyethylene glycol, titanium dioxide, magnesium stearinovokisly and dye.

The invention consists in the following.

The use of Trimetazidine as active substances normalizes the energy metabolism of cells subjected to hypoxia or ischemia, prevents the decrease in intracellular ATP content. Thus, the drug ensures the normal functioning of membrane ion channels, transmembrane transport of ions and K is the atrium and maintaining cellular homeostasis.

Trimetazidine slows down the oxidation of fatty acids by selective inhibition of long-chain 3-ketoacyl-COA thiolase, which leads to increased oxidation of glucose and to restore the coupling between glycolysis and oxidative decarboxylation and, as shown, causes myocardial protection from ischemia. Switching oxidation fatty acid oxidation to glucose oxidation is the basis antianginal action of Trimetazidine.

The composition of auxiliary components, such as mannitol, starch, microcrystalline cellulose, povidone, crosscarmellose and magnesium stearinovokisly in the stated ratios selected in such a way as to ensure high mechanical strength tablet with a small pressing force during manufacture of the dosage form, stability of the active substance during storage and rapid release of Trimetazidine in the body.

Use for the shell of such substances in the aggregate, as oksipropilmetiltselljuloza, polyethylene glycol, titanium dioxide, magnesium stearinovokisly and acid dye, each in the claimed ratio allows to obtain a durable protective shell that provides protection for the tablet during the validity period with a slight increase in the mass of the tablets.

The invention is carried out as the way.

Trimetazidine, mannitol, corn starch and microcrystalline cellulose are thoroughly mixed and moistened with a solution of povidone, mix to a uniform moisture and granularit.

The wet granules are dried at a temperature of 35-45°to a residual moisture of 2.0%.

The dried pellets are cooled to room temperature and conduct a dry granulation. The dry granulate optivault adding croscarmellose and magnesium stearinovokisly. The mixture is stirred until a homogeneous tablet mass.

Then the mass tabletirujut, receiving tablets-kernel biconvex shape with a diameter of 6.0±0.03 mm) and weight 0,1 g

For coating the tablet cores using a water suspension containing oksipropilmetiltselljuloza, polyethylene glycol 6000, titanium dioxide, magnesium stearinovokisly and dye acid red.

The application shell stop once the desired weight of the tablet. The weight of the coated tablet is 0,104,

The table shows the formulations of the claimed composition.

Table
ComponentsRecipe
123
g%% %
The kernel
Trimetazidine a dihydrochloride0,0220,0to 12.040,0
Corn starch0,02424,028,018,0
Mannitol0,01515,0of 17.0to 12.0
Povidone0,0088,09,06,0
Magnesium stearinovokisly0,0011,01,50,5
Crosscarmellose0,0033,05,01,5
Microcrystalline cellulose0,02929,027,533,0
The mass of the nucleus tablets0,1100100100
The composition of the shell
Oksipropilmetiltselljuloza0,002870,057,082,0
Polyethylene glycol 60000,000328,7510,05,0
The titanium dioxide pigment0,0006716,7525,010,0
Magnesium stearinovokisly the of 0.000061,53,01,0
Dye acid red0,000153,755,02,0
The weight of the shell0,004100100100
Weight pills0.104 g

An example of production

1.5 kg Trimetazidine dihydrochloride, 1.125 kg mannitol, 1.8 kg of corn starch and 2.1 kg of microcrystalline cellulose mix thoroughly and moisturize 3,182 kg of a solution of povidone, mix to a uniform moisture and granularit.

The wet granules are dried at a temperature of 35-45°to a residual moisture of 2.0%. The dried pellets are cooled to room temperature and conduct a dry granulation. To 7,0 kg of dry granulate add 0,225 kg croscarmelose and 0,075 kg magnesium stearinovokisly. The mixture is stirred until a homogeneous tablet mass.

Then tablets weight tabletirujut, receiving tablets-kernel biconvex shape with a diameter of 6.0±0.03 mm) and weight 0,1 g

For coating the tablet cores prepared aqueous suspension containing oksipropilmetiltselljuloza, polyethylene glycol 6000, titanium dioxide, magnesium stearinovokisly and dye acid red is output.

The shell is produced by sputtering film-forming suspension moving in a rotating perforated drum pills-cores and simultaneous drying of the formed film is fed into the machine by the heated air. Application stop when you reach the required weight of the tablet. The weight of the coated tablet is 0,104,

Experimental studies have shown that obtained in accordance with examples of the tablets have high mechanical strength at low (3.5 to 5 kN) the pressing force. The proposed structure provides a good raspadaemost form release within 30 minutes, more than 80% of Trimetazidine that allows you to achieve the greatest therapeutic effect in the shortest time.

1. Dosage form having antianginal action, consisting of a nucleus containing as active Trimetazidine a dihydrochloride and excipients, and dissolving in the stomach membrane, and the nucleus contains as excipients starch, mannitol, povidone, magnesium stearinovokisly, croscarmelose and microcrystalline cellulose, the next content, wt.%:

16,0-29,0
Trimetazidine a dihydrochloride5,0-42,0
Starch
Mannitol12,0-of 17.0
Povidone5,0-9,5
Magnesium stearinovokisly0.5 to 1.5
Crosscarmellose1,5-5,0
Microcrystalline cellulose23,0-33,0

and the shell contains oksipropilmetiltselljuloza, polyethylene glycol, titanium dioxide, magnesium stearinovokisly and dye acid red, with the following content, wt.%:

Oksipropilmetiltselljuloza57,0-82,0
The polyethylene glycol5,0-10,0
Titanium dioxide10,0-25,0
Magnesium stearinovokisly1,0-3,0
Dye acid red2,0-5,0

2. Dosage form according to claim 1, characterized in that the starch contains corn starch.

3. A method of manufacturing a dosage form having antianginal deistvie, in accordance with any of claims 1 and 2, namely, that mix Trimetazidine a dihydrochloride, mannitol, starch and microcrystalline cellulose, the resulting mixture is moistened with a solution of povidone, re-mix, damp granulation, subsequent drying, the dry granules is tion, the powder mixture croscarmellose and magnesium stearinovokisly followed by pelletizing and coating shell of an aqueous suspension containing oksipropilmetiltselljuloza, polyethylene glycol, titanium dioxide, magnesium stearinovokisly and dye.



 

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