Pharmaceutical composition having anti-fungal activity, and how you can get

 

(57) Abstract:

The invention relates to the field of medicine and is suitable for the treatment of fungal diseases, as well as for the prevention and treatment of fungal complications of antibiotic therapy. The composition includes a core and a shell. The core contains nystatin, lactose, potato starch, calcium stearate, oksipropilmetiltselljuloza, magnesium carbonate basic. The shell consists of methylcellulose, twin, titanium dioxide, paraffin oil, oksipropilmetiltselljulozy and tropeolin O. invention relates to a method of obtaining a composition that includes a mixture of nystatin with filler, wetting resulting mass is dissolved in 76% alcohol, oksipropilmetiltselljulozy. Then the extract in a water-alcohol solution, drying, granulating, dusting with calcium stearate, tableting and coating shell. The technical result of the invention is to provide a composition, stable in storage, easily releasing the active substance, which ensures its high bioavailability. 2 S. and 1 C.p. f-crystals, 1 table.

The invention relates to the field of medicine and is suitable for the treatment of fungal diseases, and the prevention and treatment of aetsa nystatin (1). Nystatin is an antifungal drug from the group of amphoteric, polienovykh antibiotics, active against yeast-like fungi of the genus Candida, as well as aspergilli.

Substance nystatin is hygroscopic and sensitive to the action of light, heat, acids and alkalis, as a result of their exposure loses its activity. This makes specific requirements for the development of dosage forms of nystatin and technologies of their production.

To protect the solid dosage form containing the active substance, namely, nystatin, and to simplify technology and.with. The USSR N1158251 1985 proposed for the deposition of a hydrophobic layer to apply a 4.8% aqueous emulsion of silicone KE-10-12 and to the outer shell - 2% aqueous methylcellulose composition. However, the composition of the coating did not ensure compliance indicator raspadaemosti the requirements of the global Fund XI. To improve raspadaemosti dosage forms silicone emulsion replaced by tween - 80 (and.with. 1569018, 1991), but its use reduces the stability of the tablet during storage, thereby reducing the shelf life of the drug.

In the industrial regulations N61-0261-2-88 on tablets nystatin 250000 UNITS and 500,000 UNITS, coated, describes the pharmacist is in the form of tablets, coated. Tablet core contains, wt%:

Nystatin - 46,29

Lactose - 31,67

Gelatin - 2,5

Talc - 2,0

Stearic acid - 0,85

Potato starch - 16,69

And a shell containing wt.%:

Methylcellulose - 78,0

Tween-80 - 10,0

Vanilla - 3,6

Titanium dioxide is 6.4

Emulsion EC-10-16 - 1,6

Pyrazolinones yellow - 0,4

The antifungal composition was prepared as follows. In the mixer load the lactose and the potato starch, mix and hydrate the starch-gelatin paste. The resulting mixture granularit, after which the granules with a particle size of not more than 5 mm is dried in the dryer with the agitator, the dried mass is milled and mixed with nystatin, talc, stearic acid to obtain the mass of the nucleus. The mass of the nucleus bitteroot, granularit, tabletirujut and put the shell.

Thus obtained pharmaceutical form has the following disadvantages:

- due to the presence in the nucleus of gelatin, poorly soluble in 76% ethanol, after 3 years of storage does not meet raspadaemosti normative values GF XI;

- part of the kernel stearic acid is not always available due to the lack of raw materials;

- t is at its content in the tablet should be strictly controlled;

on the shell of the tablets manufactured using silicone emulsion EC-10-16, during storage appears white bloom, which spoils their appearance;

- dye pyrazolinones yellow in accordance with the Order of the Ministry of health 80 from 19.03.98 was banned for use in the production of pharmaceuticals.

The invention is aimed at creating a solid dosage form that meets the requirements of the pharmaceutical agent. Dosage form should be easy to release base material, to provide high bioavailability, to be safe, to have a good appearance.

This technical result is achieved by the fact that the proposed new antifungal composition comprises a core containing the active ingredient nystatin and as excipients lactose, potato starch, calcium stearate, oksipropilmetiltselljuloza, magnesium carbonate core, and a shell consisting of methyl cellulose, tween-80, vanilla, titanium dioxide, paraffin oil, oksipropilmetiltselljulozy, tropeolin O.

The ingredients contained in the kernel in the following ratio, wt.%:

Nystatin - 41,0 - 46,26

Lactose - 28 - 1,02

Magnesium carbonate basic - 9,8 - 10,2

The claimed ratio found experimentally and provides the necessary kernel of the composition. Introduction to the composition of oksipropilmetiltselljulozy and magnesium carbonate basic leads to a decrease raspadaemosti, and therefore, increases the bioavailability core tablet while providing stability during storage and satisfactory strength.

The proposed dosage form is in the form of tablets, which has a shell. The presence of a shell of the inventive composition further enhances the stability of the composition, increases the shelf life, improves its appearance and organoleptic properties.

The optimal ratio of ingredients in the shell is, wt.%:

MC - 36,37 - 37,84

Tween-80 - 9,12 - 9.49

Vanilla - 7,84 - 8,16

Titanium dioxide - 4,51 - 4,69

Vaseline oil - 15,7 - 16,33

OPMC - 24,26 - 25,24

Tropeolin ON - 0,0755 - 0,0785

MC used as the basis of the shell, does not decompose at a temperature of 37oSince, therefore, the composition of the shell as a pore-forming entered OPMC contributing to the ease with which it can decay. The ratio OPMC to MC is 4: 6, this ratio allows the release of the active substance, that, in turn, increases the bioavailability of the drug.

In the course of the experiments, as the dye were tested yellow dye KF-6001, quinoline yellow E104, tropeolin O. color Uniformity was achieved in the application of tropeolin O.

Introduction to the composition of the oil vaseline allows you to the end of the retention period to have the tablet uniform yellow colour without white residue.

A method of obtaining a pharmaceutical composition, antifungal activity, containing nystatin and excipients, includes mixing the active substance with a filler composed of a mixture of lactose, starch, magnesium carbonate basic, hydration resulting mass is dissolved in 76% aqueous alcohol OPMC, exposure in a tightly closed vessel for removal of microbial contamination, drying, granulation, dusting with calcium stearate, tableting and coating shell.

Use as a moisturiser 76% aqueous alcohol solution OPMC allows you to get tabletow mass with good flowability and to achieve uniformity of tablet weight and strength. Simplified procedure of obtaining tablets nystatin due ish powder nystatin (417 g, the activity of 5000 IU/mg), lactose (240 g), magnesium carbonate basic (100 g), potato starch (223 g) hydrate in the mixer-granulator 450 ml of a 2.2% solution OPMC (the alcohol content in the humidifier 76%). The wetted mass is placed in a sealed package. After 24 hours, the mass is dried at a temperature of 40oWith, granularit, dry granules optivault 10 g of calcium stearate and tabletirujut. Received engine cover film cover installation fluidized bed, which is applied 3.2 g Veselinovo oil and 1000 ml film-forming composition containing 12,8 MC, 8.6 g OPMC, 1.9 grams of tween - 80, 1,7 titanium dioxide, 1 g of vanillin, 16 mg of tropeolin O. Layering continue to obtain a film, a satisfactory thickness and color depth. Get 997,2 g of tablets with an average weight 0.126 g, which has a light yellow color and meet the requirements of the pharmaceutical agent.

Example 2.

Analogously to example 1, with the difference that as a moisturizer instead of a 2.2% solution OPMC using 5% solution of acetylcellulose (AFC)

Example 3.

Analogously to example 1, with the difference that to cover the use of film-forming composition containing 10.7 g MC, 10.7 g OPMC, 1.9 grams of tween - 80, 1,7 titanium dioxide, 1 g vanisperse film-forming composition, containing 12.8 g MC, 8.6 g OPMC, 1.9 grams of tween - 80, 1.7 g of titanium dioxide, 1 g of vanillin, 13,92 mg dye KF-6001.

The resulting composition is stable during storage, easily releases the active substance, which ensures its high bioavailability.

Literature

1. Auth. St. 1158251, class a 61 K 9/00, 1983.

2. Auth. St. 1569018.

3. Industrial regulations 64-0261-2-88 into tablets nystatin and 500000 250000 U U coated. Penza plant "Biosynthesis", 1988

1. Pharmaceutical composition having anti-fungal activity, which includes a core containing the active ingredient nystatin and acceptable excipients, characterized in that the quality of excipients contains lactose, potato starch, calcium stearate, oksipropilmetiltselljuloza, magnesium carbonate basic in the following ratio of ingredients, wt.%:

Nystatin - 41,0-46,26

Lactose - 23,53-24,48

Potato starch - 18,28-19,02

Calcium stearate - 0,98-1,02

OPMC - 0,98-10,2

Magnesium carbonate basic - 9,8-10,2

and the shell is composed of methyl cellulose, tween-80, titanium dioxide, vanillin, butter vaseline, oksipropilmetiltselljulozy and tropeolin O.


MC - 36,37-37,84

Tween-80 - 9,12-9,49

Vanilla - 7,84-8,16

Titanium dioxide - 4,51-4,69

OPMC - 24,26-25,24

Vaseline oil - 15,7-16,33

Tropeolin ON - 0,0755-0,0785

3. A method of obtaining a pharmaceutical composition, described in paragraph 1, which includes the specified mixing the active substance with a filler composed of a mixture of lactose, starch and magnesium carbonate basic, moistening the mass of the water-alcohol solution of oksipropilmetiltselljulozy, extract it, drying, granulation, dusting with calcium stearate, tableting and coating shell.

 

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