Suppositories with antifungal activity

 

(57) Abstract:

The invention relates to pharmaceutical industry and relates to a suppository with antifungal activity. The invention lies in the fact that the suppositories contain nystatin, nipazol, citric acid food, hydrophilic basis for the content or complete exclusion from the composition of paraffin oil. The invention provides for the creation of antifungal suppositories, which have high pharmaceutical, technological and consumer properties. 2 C. p. F.-ly, 3 tables.

The invention relates to pharmaceutical industry and relates to the formulation of suppositories containing nystatin, an antifungal antibiotic that is highly effective against yeast-like fungi of the genus Candida and intended for the treatment of candidatesa mucous membranes of the lower bowel and vagina, as well as vulvovaginitis of obesity.

The closest in technical essence to the proposed suppositories and taken as the prototype are suppositories containing active substance, antioxidants, citric acid, vaseline oil, the base for suppositories next time is Butylacetyl - 0,00014-0,00016

Citric acid food - 0,000074-0,000076

Vaseline oil - 0,047-0,064

Hydrophobic base - Rest

option 2

Nystatin, ED - 425000-575000

Butylacetamide - 0,000074-0,000076

Butylacetyl - 0,00014-0,00016

Citric acid food - 0,000074-0,000076

Vaseline oil - 0,094-0,128

Hydrophobic base - Rest [1]

Data suppositories contain as antioxidants butylacetamide and butiloxitoluol that are currently not available. In addition, a high content of paraffin oil gives suppozitornyj mass high turnover, especially in the summer, which is not conducive to obtaining suppositories required quality in a production environment and is not always possible to keep the consumer properties of the finished product during transportation and storage.

Object of the present invention is to provide an antifungal suppositories, which have high pharmaceutical, technological and consumer properties.

This goal is achieved by the fact that antifungal suppositories containing nystatin, antioxidants, citric acid, vaseline oil, hydrophobic base, according from the partial or complete exclusion from the composition of suppositories oil vaseline in the following ratio of components, g on one suppository:

variant 1

Nystatin, ED - 212500-275000

Nipazol - 0,002

Citric acid food - 0,000075

Vaseline oil - 0-0,027

Hydrophobic base - Rest

option 2

Nystatin, ED - 425000-550000

Nipazol - 0,002

Citric acid food - 0,000075

Vaseline oil - 0-0,055

Hydrophobic base - Rest

While suppositories made in the form of rectal mass of 2 g with the activity of nystatin 2125000-275000 ED and 425000-550000 ED with the content of paraffin oil 0,027-to 0.055 g for one suppository or vaginal weight of 2.4 g with nystatin activity 212500-275000 ED and 425000-550000 UNITS and excluding oil vaseline is included.

The biological activity of nystatin is expressed in units of (ED), while it can vary from 4500 UNITS and up to 1 mg.

The calculation of the concentration of nystatin in grams in the examples of table 1 are determined from the content of 1 mg nystatin 4500 IU and 5000 IU (in terms of dry substance). If nystatin activity higher than 4500 UNITS, its quantitative content in one suppositories decreased, but the activity of one suppository should be kept within 212500-275000 ED (for suppositories 250 thousand EIG nystatin, was carried out experimentally with the identification of all factors of manufacturing technology, which can influence the improvement of the quality of the finished dosage form.

As a result of experiments it was found that of preservatives that have been tested (nipagin, nipazol, chlorocresol), the best results were achieved when used as a preservative nipazola - propyl ester peroxybenzoyl acid. Antiseptic properties and solubility in hydrophobic basis nipazol significantly superior to other preservatives. Use nipazola in the amount of 0.002 g is optimal, allows the drug to maintain their properties and microbial purity within 2 years, and the deviation from it leads to lower quality. The application of the proposed suppositories citric acid enhances the protective action of the preservative. In addition, introducing nipazola is possible to reduce the amount of oil or vaseline to exclude him from the lineup completely.

Under existing requirements, storage suppositories should be carried out at a temperature of +5oC. During transportation is not always possible to perform storage conditions, the drug Sredne properties.

When the development was proposed to reduce the amount of vaseline oil, contained in a single rectal suppositories to 0,027-to 0.055 g, and completely eliminate it from vaginal suppositories due to changes in technology making candle mass and the use of more advanced equipment.

Nystatin, citric acid, nipazol mixed with vaseline oil (in the case of preparing the masses for rectal suppositories) and part of the molten hydrophobic base, mix, grind the mixture in a colloid mill to obtain a homogeneous mass.

The resulting concentrate is gradually introduced into the remaining melted suppozitornyj basis, mix, homogeneity pass to the stage of forming suppositories

Experimentally selected temperature at the stage of forming suppozitornoj mass allows to obtain suppositories required quality, with high consumer properties: uniformity of weight, hardness, providing ease of use.

Suppositories proposed composition is tested to measure the hardness. With the aim of obtaining characteristics of hardness conducted malaconotinae measurement ASS="ptx2">

Example 1.The composition g on 1 suppository rectal mass of 2.0 g:

Nystatin - 0,0555

Nipazol - 0,002

Citric acid - 0,000075

Vaseline oil - 0,027

The basis for suppositories - Before 2

As the basis of use witepsol grades N-15 and W-35 in 1: 1 ratio. Get suppositories as follows.

Pre-melt suppozitornyj the basis of witepsol N-15 and W-35 at a temperature of 505oC. Sifted nystatin and citric acid mixed with vaseline oil, nipazola and part of the molten witepsol W-35, stirred with a stirrer for 15 to 20 minutes at a temperature of 40oWith, rubbing the resulting concentrate on colloid mill and gradually introduce it into the prepared suppozitornyj basis. The resulting mass is stirred for 10 min, then homogeneity 30-40 minutes at a temperature of 40-45oFrom, then submit to the stage of forming of suppositories.

Received suppositories have the following physical characteristics: full time deformation 5 min 05 sec; hardness of 5.9% penetration.

Example 2. The composition g 1 vaginal suppository weighing 2.4 g:

Nystatin - 0,0555

Nipazol - 0,002

Citric acid - 0,000075

The basis for suppositories - Before the 6 min 56 sec the hardness of 6.8% penetration.

Examples 3 and 4 are similar to examples 1 and 2 with the difference in content in the composition of nystatin suppositories and vaseline oil.

Example 5. The composition g on 1 suppository rectal mass of 2.0 g:

Nystatin - 0,111

Nipazol - 0,002

Citric acid - 0,000075

Vaseline oil - 0,055

The basis for suppositories - 2.4

Technology of production of suppositories corresponds to the one given in example 1. Their full deformation 6 min 13 sec, the hardness of 5.8% penetration.

Example 6. The composition g 1 vaginal suppository weighing 2.4 g:

Nystatin - 0,111

Nipazol - 0,002

Citric acid - 0,000075

The basis for suppositories - 2.4

Technology of production of suppositories corresponds to the one given in example 1. Their full deformation 6 min 19 sec, the hardness of 6.3% penetration.

Examples 7, 8 are carried out analogously to examples 5 and 6 with the difference in content in the composition of nystatin suppositories and vaseline oil.

All of the above examples are shown in table 1.

In the pharmacology laboratory of JSC "Biosynthesis" studies have been conducted irritant drugs, soteriades is 1.

Irritant effects were studied in experiments on white rats by the reaction of the mucous membrane of the peritoneum and rabbits, where it was determined irritant effect of samples on the mucous membrane of the conjunctiva of the eye.

In experiments, subjects suppositories with nystatin was melted in a water bath at a temperature of 37-38oC. the Molten test sample of a medicinal product in the amount of 0.5 ml per animal were injected white rats vnutribryushnoe. After 30 min, the animal was killed and cut open the abdominal cavity. On the preparations of the peritoneum and mesentery taken all runs of the experiment, not detected significant changes in their mucosa as compared with intact animals.

To assess the irritant suppositories with nystatin on the mucous membranes of the conjunctiva of the eyes of rabbits, conjuctival eye bag was introduced 2 drops of molten mass of the suppository. The other eye was a test. In all series of experiments mucosa was hyperemic, slightly narrowed palpebral. The vascular network of the sclera was not changed. Such phenomena sopranos throughout 60-70 minutes Then restored the original color of conjunctiva and normal is selected and vaginal suppositories, made on the proposed formulations during storage. As can be seen from the tables, the claimed suppositories, deposited, kept the original properties within 2 years.

Sources of information

1. Patent N 2139707, A 61 K 9/02, 24.12.1996.

2. Bolshakov Century. N. Excipients in pharmaceutical forms. Leningrad, 1991, page 12.

3. Mashkovsky M. D. Drugs, so 2, Kharkov: Torsing, 1998, page 287.

1. Suppositories with antifungal activity, containing nystatin, citric acid food preservative and a hydrophobic base, characterized in that as preservatives contain nipazol content or complete exclusion from the composition of paraffin oil in the following ratio of components, g on one suppository:

Nystatin, ED - 212500 - 275000

Nipazol - 0,002

Citric acid food - 0,000075

Vaseline oil - 0 - 0,027

Hydrophobic base - Rest

2. Suppositories with antifungal activity, containing nystatin, citric acid food preservative and a hydrophobic base, characterized in that as preservatives contain nipazol content or complete exclusion from the composition of the M0

Nipazol - 0,002

Citric acid food - 0,000075

Vaseline oil - 0 - 0,055

Hydrophobic base - the Rest

 

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