Antibacterial pharmaceutical composition and method of reception

 

(57) Abstract:

The composition comprises as active ingredient a therapeutically effective amount of erythromycin and as the target additives, % by weight of erythromycin: starch 40,95-71,33, polyvinylpyrrolidone 3,53-4,77, tween-80 2,78-3,84 and salt of stearic acid 1,39-1,95. Tablet-core is covered with a film-forming shell. The shell is made from a mixture of acetylcellulose, castor oil, and titanium dioxide. The method of producing tablets is carried out by wet granulation with subsequent coating of the tablet cores of the film-forming composition. Tablets coated erythromycin meet all the requirements of Gasfurnace X1, easily release the active ingredient that provides high bioavailability of erythromycin. The shelf life of erythromycin tablets is not less than two years. 2 S. and 6 C.p. f-crystals, 1 table.

The invention relates to medicine, specifically to antibacterial substance erythromycin.

Erythromycin is an antibiotic produced by Streptomyces erythreus or other related microorganisms. He is one of the first antibiotics-macrolides included in medical practice. Erythromycin is effective against gromacki, meningococci); also works for Brucella, rickettsiae, causative agents of trachoma, and syphilis; little or no effect on most gram-negative bacteria, mycobacteria, small and medium-sized viruses, fungi. In therapeutic doses erythromycin bakteriostaticheski.

Although in recent years a group of antibiotics-macrolides significantly expanded and created a number of semi-synthetic macrolides, superior therapeutic efficacy of the first antibiotics, macrolides, erythromycin has not lost its value and is still widely used in medical practice for the treatment of pneumonia, pnevmatikatos and other pulmonary diseases; in septic conditions, an erysipelatous inflammation, mastitis, osteomyelitis, peritonitis, purulent otitis and other pyoinflammatory processes; in the treatment of gonorrhea, syphilis, prevention and treatment of rheumatism and other

Erythromycin was first protected by a U.S. patent 2653899, 1953, which describes erythromycin-base, its salts and method of its production. No dosage forms in the patent referred to.

Identification of high antimicrobial activity of erythromycin led to the creation of a variety of dosage forms on the basis of the er is s and solutions ointments, candles. Most common in medical practice have found tablets erythromycin 0.1 g 0.25 g, coated (Mashkovsky, M. D. "Medicines", "New Wave", 2000, so 2, page 259).

In U.S. patent 3485914, 1969, describes a method for a pharmaceutical product containing the antibiotic sustained therapeutic effect, and the preparation obtained in this way. The drug is designed for oral administration, in the form of pellets, containing the core of a mixture of antibiotic, polyvinylpyrrolidone or shellac, and a shell covering the core, consisting of polyvinylpyrrolidone or shellac. The weight ratio of the antibiotic, polyvinylpyrrolidone or shellac 10:0,9-1,2:0,4-0,6. The core may contain a filler is talc or silica, or a mixture. Every gram of granules contains 550-700 mg antibiotic. The preferred antibiotic is erythromycin and its salts. The disadvantage of this drug is slowly coming therapeutic effect, and the use of separate legacy ingredients (e.g., shellac).

In U.S. patent 3865935, 1975, describes a tablet form of erythromycin in the form of a solid enteric-resistant form containing: (a) granules comprising er acidic environment, b) anhydrous sodium citrate or citrate dihydrate sodium, b) at least one lubricating agent, d) at least one separating agent.

The ingredients are mixed in the following ratio: 5 to 20 parts binder (mainly, polyvinylpyrrolidone or hypromellose); 12-35 parts dezintegriruetsja agent (mainly microcrystalline cellulose, starch, methylcellulose, carboxymethylcellulose, talc); 0-0,16 parts buffer (caustic sodium, sodium hydroxide) together with 0-0,8 parts of sodium phosphate (phosphate of potassium); 100 parts eritromicina Foundation. Dry granules are combined with the following additives: granules with erythromycin - 320 parts, dihydrate sodium citrate - 300 pieces, amberlite IRP-88 - 15 parts magnesium stearate 3 parts. The mixture tabletirujut. Indicated that the tablets produced an immediate action after hitting the gastrointestinal tract. The disadvantage of these pills is the short shelf life of 9 months.

In U.S. patent 4340582, 1982, describes erythromycin tablets with a coating soluble in the intestine. The core contains 250 parts base erythromycin in the form of its dihydrate, 35-100 parts are water soluble non-toxic salts for oral administration and 40-165 Thu use polyvinylpyrrolidone, microcrystalline cellulose, sodium citrate, polysaccharides (lactose), talc, corn starch, amberlite IRP-88. The core is covered with a sheath, which is applied from a solution 16-25 parts of phthalate hydroxypropylmethylcellulose in a mixture of ethanol and water that contain dyes, pigments, plasticizers and flavourings. Due to the fact that in recent years become stricter requirements for the quality of medicines, new quality indicators in foreign pharmacopoeias, and especially in Gasfurnace XI ed., tablets erythromycin described in U.S. patent N 4340582 not meet all the requirements.

The objective of the invention is to provide an antibacterial pharmaceutical compositions on the basis of erythromycin, satisfying all the requirements of Gosfarmakapei XI edition, which has high bioavailability and shelf life of not less than two years.

This is achieved antibacterial pharmaceutical composition comprising as active ingredient a therapeutically effective amount of erythromycin, specially selected additives target (leavening agents, binders), and the tablet cores coated with enteric-soluble shell.

As the target issue for lighting the AI components, % by weight of erythromycin:

Starch - 40,95-71,33

Polyvinylpyrrolidone - 3,53-4,77

Tween-80 - 2,78-3,84

Salt of stearic acid - 1,39-1,95

Starch is preferable to use potato and/or corn; polyvinylpyrrolidone preferred high molecular weight, as well as salts of stearic acid, magnesium stearate and/or calcium.

Antibacterial pharmaceutical composition is made in solid form, mostly in the form of tablets, coated.

The shell includes the following ingredients, grams per 1 tablet-core:

Acetylcellulose - 0,00925-0,01483

Castor oil - 0,00054-0,00595

Titanium dioxide - 0,00085-0,00398

The claimed ratio of the components found experimentally, is optimal and allows to obtain a technical result that is appropriate to the task: tablets erythromycin meet all the requirements of Gosfarmakapei XI ed., regulatory requirements on erythromycin, have high bioavailability and shelf life of not less than two years (see table).

One way of getting of pills is a method of wet granulation, comprising the following steps: mixing powders, moisturizing, shmesani the HP, M.: Medicine, 1991, S. 142).

The method of producing tablets erythromycin is as follows: the mixture of powders erythromycin, polyvinyl pyrrolidone, starch moisturize first 33% solution of tween-80, then a 5% starch paste and passed through the granulator. The moist granulate is dried at 55-60oWith up to a residual moisture of 3-5%. The dried granules are passed through a granulator, milled granules optivault mixture of starch and salts of stearic acid and tabletirujut on a tablet machine. Tablets-engine cover film-forming composition consisting of a mixture of acetylcellulose dissolved in a mixture of acetone and alcohol, titanium dioxide, and castor oil. All this together gives the opportunity to get tablets erythromycin, corresponding to all requirements of Gosfarmakapei XI of editions of the normative documents on erythromycin, easily, releasing the active substance, which ensures its high bioavailability, and at the same time, the shelf life of the tablets is not less than two years (see table).

The following examples illustrate the invention.

Example 1. Mix the powders 103,2 g of erythromycin, 4,47 g of polyvinylpyrrolidone and 60.0 g of corn starch, mix up one of 3.4 g of corn starch) and then doublenaut water in an amount of 8 ml The resulting mass is thoroughly mixed and passed through a granulator. The moist granulate is dried at 55-60oWith up to a residual moisture of 3-5%, the dried granules are passed through a granulator. The resulting mass optivault a mixture of 2.5 g of corn starch and 1.8 g of magnesium stearate, ready tablets weight tabletirujut on a tablet machine. Get 385 tablets with a total weight of 173,1 g and the content in one tablet 0,g% erythromycin. The obtained kernel is applied film-forming composition containing gomogenizirovannogo mixture at 5,182 g acetylcellulose dissolved in a mixture of 75.0 g of acetone and of 19.4 g of alcohol, 2,076 g of castor oil and KZT 1,394 g of titanium dioxide. Layering continue to obtain satisfactory film thickness. The obtained tablets meet all regulatory requirements, have high bioavailability and shelf life of more than two years (see table).

Example 2. Obtaining tablets erythromycin carried out as in example 1, on the basis of 103,2 g of erythromycin, 60,3 g of potato starch, 4,035 g polyvinylpyrrolidone, 3.25 g of tween-80, 1.64 g of magnesium stearate. Receive 387 tablets-cores with a total weight of 166,4 g and the content in one tablet 0,261 g 1,8% erythromycin. The obtained tablet cover film-forming status the tablet on all indicators meet all regulatory requirements (see table).

Example 3. Obtaining tablets erythromycin carried out as in example 1, on the basis of 103,2 g of erythromycin, is 73.5 g of potato starch, 4.9 g of polyvinylpyrrolidone of 3.95 g of tween-80 and of 1.97 g of calcium stearate. Get 385 tablets with a total weight of 180,96 g and the content in one tablet 0,2491,5% erythromycin. The obtained tablets-engine cover film-forming composition containing 5,706 g acetylcellulose, 1,105 g of castor oil and 1,532 g of titanium dioxide. The obtained tablets comply with all regulatory requirements for all indicators (see table).

1. Antibacterial pharmaceutical composition in solid dosage form consisting of a coated film-forming nuclear envelope, containing a therapeutically effective amount of erythromycin and targeted supplements, including polyvinylpyrrolidone and starch, characterized in that it further comprises tween-80 and a salt of stearic acid with the following composition of the target additive kernels, % by weight of erythromycin:

Starch - 40,95 - 71,33

Polyvinylpyrrolidone - 3,53 - 4,77

Tween-80 - 2,78 - 3,84

Salt of stearic acid - 1,39 - 1,95

2. The composition according to p. 1, characterized in that the starch it contains potato and/is idona it contains high-molecular polyvinylpyrrolidone.

4. Composition according to any one of paragraphs. 1-3, characterized in that salts of stearic acid it contains magnesium and/or calcium salt.

5. Composition according to any one of paragraphs. 1-4, characterized in that it is made in the form of tablets.

6. Composition according to any one of paragraphs. 1-5, characterized in that the shell has the following ingredients g per tablet-core:

Acetylcellulose - 0,00925 - 0,01483

Castor oil - 0,00054 - 0,00595

Titanium dioxide - 0,00085 - 0,00398

7. The method of obtaining the antibacterial composition in tablet form, wherein upon receipt of a composition described in any of paragraphs. 1-6, mix therapeutically effective amount of erythromycin with polyvinylpyrrolidone and starch, moistened mixture first 33% solution of tween-80, then a 5% starch paste, granularit, dried wet granulate, conduct a dry granulation, the powder mass mixture of starch and salts of stearic acid, tableting and coating of tablets film-forming cores sheath made from a mixture of acetylcellulose, castor oil, and titanium dioxide.

8. The method according to p. 7, characterized in that the drying of wet granules is carried out until the mod is

 

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