RU2153875C2 - Pharmaceutical composition and method of its preparing - Google Patents

Abstract

FIELD: medicine, pharmacology, pharmacy. SUBSTANCE: invention relates to pharmaceutical composition as tablets based on acetyl-salicylic acid that has components taken in the definite ratio. EFFECT: prolonged fitness period, improved strength indices, simplified method of making. 2 cl, 1 tbl, 6 ex

Description

 The invention relates to the pharmaceutical industry and relates to a method for producing tablets based on acetylsalicylic acid.

Known methods:
- obtaining an aqueous solution of acetylsalicylic acid, carried out by mixing acetylsalicylic acid (ASA) and hexamethylenetetramine with the addition of water at a ratio of (1: 1) - (1; 4) [1. A. s. USSR N 1489012, MKI A 61 K 31/60, chipboard];
- obtaining effervescent tablets by separate granulation of sodium bicarbonate, an organic acid treated with a 10-30% paraffin solution with an emulsifier No. 1, and 5-15% anhydrous magnesium or sodium sulfate is introduced into the granulate of the drug levoridone [2. A.S. USSR N 1155268, MKI A 61 K 9/22, Bull. N 18, 1985];
- obtaining tablets of an acid-containing agent by separate granulation of sodium bicarbonate and an acid-containing substance, mixing granules and tabletting, characterized in that, in order to eliminate side effects, granulate sodium bicarbonate and aspirin 2-4 times, moistening the obtained granules with starch paste in a ratio of 1: 0 5 - 1.0 [3. A.S. USSR N 1572629, MKI A 61 K 9/20, Bull. N 23, 1990 - prototype for the method].

 The disadvantages of the known methods for producing tablettable formulations are the stages of wetting (wetting), granulating the compositions as a whole or in stages, drying the granulate.

 A known composition comprising 89.28 wt.% Acetylsalicylic acid, 8.42 wt.% Microcrystalline cellulose, 2.24 wt.% Croscarmellose sodium and 0.24 wt.% Colloidal silicon dioxide [4. Technological regulations of production. Registration N 39. 1996 - a prototype for the composition].

 Tablets based on this composition have insufficient strength properties, have a shelf life of 2 years.

 The basis of the invention is the task of improving the composition suitable for oral use, and a method for producing a tablet form of the drug by direct compression of mixtures of 5 components prepared in a specific combination and sequence that provide physicomechanical properties and extend the shelf life of tablets without stages of wetting, granulation and drying.

The problem is solved due to the fact that the pharmaceutical composition and method for its preparation include
- mixing 89.28% of the active ingredient - acetylsalicylic acid with 7.42% of the filler is microcrystalline cellulose (mixture 1),
- mixing 2.24% baking powder - croscarmellose sodium with 0.24% colloidal silicon dioxide (a substance that provides the necessary flowability of the mixture), grinding and sieving the mixture at an impeller speed of 1000 vol. / min to obtain particles with a size of 0.6 mm (mixture 2),
- mixing the mixture 1 with a mixture of 2 and 0.3-1.0% stearic acid (a moving agent) and subsequent direct pressing.

 Examples of the proposed composition and method for its preparation.

 Example 1

 To obtain 1 million tablets based on acetylsalicylic acid with an active substance content of 325 mg, 325 kg (89.28%) of acetylsalicylic acid (ASA) and 27 kg of microcrystalline cellulose (CMC) are loaded into V- shaped mixer, stirred for 5 min at a speed of 14 vol. / min and get a mixture of 1. Croscarmellose sodium (KKN) in an amount of 8.14 kg (2.24%) and 0.86 kg (0.24%) of colloidal silicon dioxide (DCC) is loaded into a drum type mixer, stirred for 5 min at a speed of 14 rpm and sent to a grinder-grinder, where at a speed of impeller 1000 rpm the mixture is sifted through a N 610 sieve (0.6 mm perforation; free section between the impeller and the mesh 23%) to particles with size 0, 6 mm to form a mixture of 2. Then a mixture of 2 and 3.0 kg (0.82%) of stearic acid is charged to mixture 1 in a V-shaped mixer for stirring for e 5 min at a speed of 14 rpm to a particle size of 0.6 mm The resulting mixture is tableted.

 Each tablet measuring 10.32 x 4.45 mm has a biconvex shape. Relative humidity in the production room is 21-24%. Comparative characteristics are given in the table.

 Example 2. Analogously to example 1.

 Stearic acid is administered 3.66 kg (1%). Relative humidity in the production room> 24% <40%.

 Comparative characteristics are given in the table.

 Example 3. Analogously to example 1.

 Stearic acid is administered 1.1 kg (0.3%). Relative humidity in the production room> 8% <21%. Comparative characteristics are given in the table.

Example 4 is a prototype. Take 100.0 g (54.05%) of aspirin, add 10.0 g of dry starch, mix thoroughly, moisten with 5% starch paste, pass through a granulator and dry the granules at a temperature of 50 ^o C. Dried granules re-moisturize 5% starch paste, passed through a granulator and the granules are again dried at a temperature of 50 ^o C.

 The granulation process is repeated one more time. After that, the dried material is passed through a granulator and fine particles are sieved from the dry granules, then 75.0 g (40.54%) of sodium bicarbonate (GKN) are taken, and granulated in the indicated manner 3 times. The obtained dry, uniform granules of aspirin and sodium bicarbonate are combined, talc is added within 3%, mixed and tabletted. Get 370 pcs. tablets of 0.5 g [3. Example 1].

 Example 5 is a prototype. Analogously to example 1. Stearic acid is not administered. Comparative characteristics are given in the table. When pressing, the mixture sticks to the punches, the tablet is deformed, 5% of marriage.

 The addition of stearic acid less than 0.3% (0.1-0.25%) wt. inefficient. The results are similar to example 5.

 Example 6. Analogously to example 1. Stearic acid is introduced 1.1-1.3%. Comparative characteristics are shown in the table.

 The introduction of stearic acid more than 1.0 wt.% (Example 6) leads to an increase in the expenditure coefficient without improving the properties of the drug.

 The introduction of stearic acid in mixture 1 or mixture 2 affects the compressibility of the tablet mass, tablets are obtained with a deformed (damaged) surface.

 A decrease in speed to 800 rpm on the crusher-grinder during the sifting of the components of the mixture 2 leads to an increase in particle diameter up to 1 mm At the stage of tabletting, the matrices are filled unevenly with the mixture, and the tablets are broken up by weight. The tablet becomes marbling, i.e. heterogeneity, which is unacceptable in accordance with the requirements of scientific and technical documentation (NTD).

 An increase in speed to 1200-1500 rpm leads to an increase in dust formation. Compressibility of the composition worsens, tablet strength decreases. 18-50% of fine powder is lost by dust removal. According to NTD - losses should not exceed 2%.

 As can be seen from the table, the proposed pharmaceutical composition and method for its preparation (examples 1-3), compared with the known ones (examples 4, 5), can extend the shelf life of the drug, improve its strength characteristics and simplify the method of obtaining the drug based on acetylsalicylic acid.

Claims (1)

1. A pharmaceutical composition in the form of tablets, including acetylsalicylic acid, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, characterized in that it additionally contains stearic acid in the following ratio of ingredients, wt.%:
Acetylsalicylic acid - 89.28
Microcrystalline cellulose - 7.24 - 7.94
Croscarmellose sodium - 2.24
Colloidal silicon dioxide - 0.24
Stearic acid - 0.30 - 1.00
2. A method of obtaining a pharmaceutical composition in the form of tablets by mixing the active ingredient with excipients, grinding, sieving and pressing, characterized in that acetylsalicylic acid and microcrystalline cellulose are mixed before direct compression, forming a mixture of 1, crushed and sieved at an impeller speed of 1000 rpm pre-mixed croscarmellose sodium and colloidal silicon dioxide to achieve a particle size of 0.6 mm to form a mixture of 2, the resulting mixture of 1 and 2 are mixed with thearic acid.

Images