The method of producing tablets of combined drug trimethoprim with sulfamethoxazole

 

(57) Abstract:

The invention relates to the production of pharmaceutical preparations, effective for infections of the respiratory tract, urinary tract, gastrointestinal tract, surgical infection and other infectious diseases. Provide a consistent mixture of trimethoprim with auxiliary substances pre - cooked mixture of starch and lactose, and then with sulfamethoxazole. The resulting mixture is moistened granulating liquid - 10% aqueous solution of polyvinylpyrrolidone having a molecular weight of 25000-40000. This is followed by wet granulation, drying, dry granulation, the powder by sequential mixing of dry granulate with ground substandard tablets and calcium stearate, and tableting. The technical result consists in the disposition of non-conforming products, the introduction of a substance that softens the taste of the tablets, by reducing the number of auxiliary substances, while maintaining strength and raspadaemosti tablets.

The invention relates to the production of solid forms of anti-bacterial combined preparations containing derivative diaminopirimidina - trimethoprim and Sugita, urinary tract, gastrointestinal tract, surgical infection and other infectious diseases.

In 1961, it was shown antimicrobial activity of trimethoprim, and in 1965-1967, he was released the combination drug trimethoprim with sulfamethoxazole - bactrim. The principle of action of the drug is based on the braking components of the synthesis necessary for microorganisms of the vitamin folic acid. Resistance to the drug develops slowly and weakly, because of the combined composition. Bactrim (Biseptol, cotrimazole and other) comes in tablets for adults and children, respectively, containing 20 or 80 mg of trimethoprim and 100 or 400 mg of sulfamethoxazole (Chernomordik A. B. the Use of antibiotics and other chemotherapeutic drugs. Guide, Kiev, visa school, 1988, S. 161-162).

A method of obtaining tablets of combined drug trimethoprim with sulfamethoxazole by mixing the active substances trimethoprim and sulfamethoxazole with auxiliary substances and moisture mixture of an aqueous or alcoholic solution chilosi - granulating liquid (FR 2321893 But, 1976). The number of auxiliary substances is about 40% of that increase is they to the invention is a method of obtaining tablets of combined drug trimethoprim and sulfamethoxazole tablets, obtained in this way, which is a mixture of active substances trimethoprim and sulfamethoxazole with excipients, granulating, drying, dusting and pelletizing, and dusting spend a mixture of starch with calcium stearate or magnesium (EN 2141823 C1, 1997). In the patent there is no indication about what is granulating liquid, molecular weight polyvinylpyrrolidone (PVP) used in the composition of auxiliary substances, also not shown. The number of auxiliary substances is 18,82-19.93 per wt.%. It is shown that auxiliary substances, which carry a mixture of active substances are starch and PVP; granules exposed to pelletizing, contain in addition a "substrate" of the hydrolyzed starch. Tablets do not contain substances, mitigating their taste. In addition, when the inevitable production is the formation of some substandard tablets whose disposal in a known manner not provided.

An object of the invention is to reduce the total number of listed excipients and introduction at the expense of the substance that softens Neplatny the taste of the tablets and the disposal of non-conforming item is thetsa fact, in the method of producing tablets of combined drug trimethoprim with sulfamethoxazole by mixing the active substances trimethoprim and sulfamethoxazole with auxiliary substances, mixing the resulting mixture with a granulating liquid, wet granulation, drying, dusting and pelletizing consistently carry out the mixture of trimethoprim with auxiliary substances pre - cooked mixture of starch and lactose, and then with sulfamethoxazole, as granulating liquid used 10% aqueous solution of PVP having a molecular weight of 25000-40000, after drying spend additional dry granulation, and the dusting implement sequential mixing of dry granulate with ground substandard tablets and calcium stearate.

The experiments showed that the PVP molecular weight, beyond these (less than 25,000 and more than 40,000) can not only dramatically reduce the strength of the tablets, but also adversely affect the rate of release of the active substance.

The total number of auxiliary substances, including milk sugar, is in the method according to the invention is about 25 wt.% on the table is about, some of the auxiliary substances used for dusting, replaced by ground substandard tablets (about 0.48 wt.% on the tablet), which allowed us to avoid having waste.

This change in the composition of the pharmaceutical composition was only possible thanks to the new technology of preparation of tablets.

The method can be used for any permitted GF XI starch, preferably potato.

The color of the tablets is determined by the color components of the pharmaceutical composition. So, sulfamethoxazole firm Virchow, laboratories LTD, India and firms "Siris LTD, India is characterized as a white or almost white crystalline powder, and trimethoprim firm Dong Ha farm. The Indus. Co. LTD., Korea - white or yellowish-white powder. So ready tablets according to the invention ("Deceptor") are characterized as "white or white with white shade colors. Appearance of the tablets comply with the requirements of the global Fund XI, vol.2, S. 154.

The average weight of the tablets with a dose of 0.12 g (0.1 sulfamethoxazole and 0.02 g of trimethoprim), intended for children up to 12 years old, is from 0,154 to 0,166 g, and with a dose of from 0.48 g (0.4 g of sulfamethoxazole and 0.08 g of trimethoprim) - from 0.62 to 0.68,

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The invention is illustrated by the following example.

EXAMPLE 1.

In the dryer bin loaded potato starch with moisture content of 18%, dried at 50oWith over 4.5 h to a moisture content of 5% and sift. PVP with a molecular weight of 35,000 is dissolved in water at 65oC and stirring for 15 min to obtain a homogeneous transparent 10% solution.

In the mixer load sifted sulfamethoxazole in number 17,62 kg In a separate container mix 2,19 kg of dried and sifted potato starch, 3,71 kg sieved lactose. Sifted trimethoprim (3,56 kg) tracuriroot with the mixture of starch and lactose. Then trituration mixture in the mixer, stirred for 10 min and then with stirring moistened with a solution of PVP. After stirring for 5 min receive humidified mass, which is passed through a granulator with a hole diameter of 1.2 mm drum, laid out on trays and sent for drying.

The wet granulate is dried in a tray dryer for 14 h at 45oWith, stirring occasionally, until a residual moisture content of 2.0%. Then the dried mass is passed through a granulator with diameter from the ground substandard tablets. The contents stirred for 12 min, add 0,255 kg sieved calcium stearate, stirred for further 2 min and unload.

Tableting is performed on a rotary press, for tablets "Deceptor" 0.12 g - punches with dumetorum 8 mm flat punches with chamfer without risks; for tablets "Deceptor" 0,48 g - punches 13 mm flat punches with risk and chamfers. In the bunker of the press fall asleep 3 kg of the mixture and begin to pelletizing. The filling is carried out on the release of the bunker. The obtained tablets are discarded under the pull of the fume hood through a metal sieve from dust, rejected substandard tablets. Conforming tablets have the face shape, solid edge, a smooth, uniform surface and sufficient strength mechanical influences. Substandard tablets are collected in a separate container and sent for grinding in a ball mill. The obtained tablets meet the Fund 42-0055-0364-00, GF XI, vol.2, S. 154. The output stage receiving the tablets 98,74 %. Raspadaemost tablets in the aquatic environment 11 minutes Tests on the dissolution of the stable.

The method of producing tablets of combined drug trimethoprim with sulfamethoxazole by mixing the active substances trimethoprim and sulfametoxazol the modeling, drying, dusting and tabletting, characterized in that sequentially perform a mixture of trimethoprim with auxiliary substances pre - cooked mixture of starch and lactose, and then with sulfamethoxazole, as granulating liquid used 10% aqueous solution of polyvinylpyrrolidone having a molecular weight of 25000-40000, after drying spend additional dry granulation, and the dusting implement sequential mixing of dry granulate with ground substandard tablets and calcium stearate.

 

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