The method of obtaining medicines on the basis of theophylline

 

(57) Abstract:

The invention relates to medicine, specifically to the means of treatment of obstructive States. The invention consists in a method of producing a medicinal product on the basis of theophylline by mixing the dry powder composition of the polymeric carrier, which represents an interpolymer complex of polymethacrylic acid and polyethylene glycol. Next, the resulting mixture is dried to a residual moisture content of not more than 1%, granularit by sifting through a sieve, followed by dusting with calcium stearate and pelletizing. The technical result of the invention is to develop a simpler method of obtaining funds, and obtaining a more stable end product. 1 C.p. f-crystals, 1 table.

The invention relates to the field of pharmaceutical industry and relates to a method of obtaining drugs prolonged action, containing as active principle theophylline.

Theophylline is the most common currently bronchodilators tool used in various forms of bronchial obstruction, including bronchial the Naya asthma is one of the most common human diseases.

So, the American national Institute of heart, lung, and blood lead data that more than 10 million Americans have chronic obstructive pulmonary disease. The current economic and environmental conditions determine disappointing forecasts for prevalence of asthma - presumably increase by 1 -2% per decade /Therapeutic archive, 1987, 10, c.111-116/.

In this regard, the receiving effective anti-asthma resources, develop forms for their introduction, and improvement of ways to get existing product and has now the actual value.

Among bronhodilatiruyuschego drugs that can be used for different groups of patients, a significant place is occupied by structures on the basis of theophylline with prolonged action, including in the form of solid dosage forms. The intake of 1-2 tablets similar drugs provides a constant drug concentration in the blood during the day. This is especially important for people suffering from night time asthma attacks. Constant concentration of drug in the blood can significantly improve the course of bronchial asthma. In patients receiving prolon the e auxiliary substances, providing a prolonged, controlled action of theophylline, different authors have proposed different natural and synthetic polymers: vinyl, silicone, acrylic, various cellulose derivatives, etc.

For example, a method of obtaining prolonged dosage forms of theophylline by granulation of theophylline, acetotartrate cellulose with a solution of polyvinylpyrrolidone in ethanol, drying, sifting, adding polyvinyl acetate, moving, mixing and compaction /U.S. patent 4837032 And 06.06.1989/.

Also known is a method of obtaining extended compositions on the basis of theophylline by obtaining granules with a solvent, removing the solvent, adding the polyvinyl chloride in the form of a solution, drying, adding magnesium stearate and pressing /EP 239481 A2, 30.09.1987/.

Obtained by the above methods, medicines provide prolonged release of active substances, but sufficient speed control there is no selection.

Closest to the developed method is a method of obtaining a bronchodilator on the basis of theophylline in the form of tablets by wet granulation in a mixture with interest the Oia, followed by dusting with calcium stearate and pelletizing /patent RF 2097036 C1, 27.11.1997/. The resulting tool provides controlled release of theophylline and its constant concentration in the blood within 12-24 hours, However, the use of wet granulation at reception of tablets has several disadvantages: the negative impact of moisture on the drug and excipients; deterioration raspadaemosti tablets; the need to use special equipment; the duration and intensity of the process.

The present invention is to simplify the method and the improved stability of the final product.

The problem is solved by providing a method to obtain funds on the basis of theophylline by making its mixture with composite polymer carrier (CIT), which is a complex of poly (methacrylic acid and polyethylene glycol, drying the mixture to a moisture content of not more than 1%, dry granulation, injection of calcium stearate and tableting.

The proposed method has several advantages: reduction of the number of manufacturing operations and their duration, reduced complexity, reduced energy consumption, lower production costs and increase the stability of the final product.

Here is a more active beginning.

Composition per tablet presented in the table.

The technological process consists of the following stages:

- preparation of raw and auxiliary materials;

- drying a mixture of theophylline and composite polymer carrier (CPN-1);

dry granulation;

- getting tableting mass;

- tableting.

Preparation of raw and auxiliary materials.

Composite polymeric carrier during sifting strongly electrified, which leads to large losses and makes the process time consuming. Mixed with theophylline, he almost never electrified and easily screened. Given this factor, theophylline mixed with CIT in a predetermined ratio and sift together through a sieve 0,63 mm calcium Stearate is sifted through a sieve of 0.2.

Drying

For each tableting preparation this phase is of great importance. If a wrong selection of the drying process is possible sticking weight to punches, non-uniform mass distribution in the matrix, reducing the strength of the disturbed region.

According to the proposed method the mixture of theophylline and composite polymer carrier is dried to a residual moisture of not more than 1% at temperatures up to 60o60oC.

Dry granulation

Typically, the dry granulation is carried out using solutions of adhesive substance or by means of a preliminary framework of special presses.

The proposed method avoids unwanted moisture and briquetting. Applying the dry powder composite polymer carrier, it is possible to provide the necessary adhesion of the particles tableting mass during pressing.

The dried mixture of theophylline with CPN granularit by sieving through a sieve of 1.0 mm

Getting tableting mass

The resulting mixture was dried granules are mixed, optivault by adding as an anti-friction substance calcium stearate and again mix.

Tableting

The resulting mass tabletirujut on a rotary press RTM-41 M with a diameter of 12 mm punches for tablet weight 0,42 (dose 0.3 g), 10 mm tablet weight 0.28 g (dose of 0.2 and 8 mm for tablets 0.14 g (dose 0.1 g).

During tabletting periodically check the average weight of the tablets, appearance, durability and sizes.

Get tablets white color, odorless, meet the requirements of the global Fund XI.

Average weight tablet ojciwi to the effects of mechanical loads, not wear out during packaging and transportation, during long-term storage keep the indicators raspadaemosti.

The abrasion resistance of the obtained tablets was determined using the instrument of a drum type, is 98%.

When tested for solubility using as solvent liquid of 0.1 n hydrochloric acid solution in water was found that the release of theophylline is gradually reaches its maximum (approximately 85%) after 6 o'clock

Thus, the proposed method provides receiving drugs prolonged action of high quality at lower cost, and can be widely used in chemical and pharmaceutical industry.

1. The method of obtaining drugs prolonged action, characterized by the fact that theophylline is mixed with a dry powder composition of the polymeric carrier, which represents an interpolymer complex of polymethacrylic acid and polyethylene glycol, the mixture is dried to a residual moisture content of not more than 1%, granularit by sifting through a sieve, followed by dusting with calcium stearate and pelletizing.

2. FPIC is the atur 55-60oC.

 

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