Method for preparing pharmaceutical microcapsules of cephalosporins

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical microcapsulation of cephalosporins related to β-lactam antibiotics. As a microcapsule shell, the method of pharmaceutical microcapsulation of cephalosporins uses konjac gum; the microcapsules are prepared by physical-chemical technology implying the precipitation in a non-solvent using two precipitants - carbinol and diethyl ester in ratio 1:3; the method is conducted at 25°C with no special equipment.

EFFECT: invention provides simplified and accelerated preparation of the water-soluble pharmaceutical microcapsules of cephalosporins in konjac gum, loss reduction in preparing the microcapsules (higher yield-mass).

3 ex

 

The invention relates to the field of microencapsulation of drugs of cephalosporin group related to β-lactam antibiotics, in Konakovo gum physico-chemical method for the deposition aristotelem.

Previously known methods for producing microcapsules of drugs. Thus, in U.S. Pat. 2092155 IPC A61K 047/02, A61K 009/16 published 10.10.1997 Russian Federation proposed a method for microencapsulation of drugs, based on the use of special equipment use of irradiation with ultraviolet rays.

The disadvantages of this method are the duration of the process and the use of ultraviolet radiation, which can influence the formation of microcapsules.

In Pat. 2101010 IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19 Russian Federation published 10.01.1998 proposed chewable form of the drug with taste masking, having the properties of a controlled release drug product that contains microcapsules with a size of 100-800 microns in diameter and consists of pharmaceutical kernel crystalline ibuprofen and polymeric coating comprising a plasticizer, elastic enough to resist chewing. The polymer coating is a copolymer based on methacrylic acid.

The drawbacks of the invention: the use of a copolymer based on methacrylic acid, as these polymer coatings can cause cancer; complexity; the duration of the process.

In the article "Razrabotka microencapsulated and gel products and materials for various industries", Russian chemical journal, 2001, .XLV, No. 5-6, s-135 is described a method of producing microcapsules of drugs by the method of gas-phase polymerization, since the authors considered unsuitable method of chemical koatservatsii from aqueous media for microencapsulation of drugs due to the fact that most of them are water-soluble. The process of microencapsulation by the method of gas-phase polymerization using n-xylylene includes the following basic stages: evaporation dimer n-xylylene (170°C), thermal decomposition of it into the pyrolysis furnace (650°C at a residual pressure of 0.5 mm Hg), the transfer of the reaction products in the "cold" chamber of polymerization (20°C, the residual pressure of 0.1 mm Hg), deposition and polymerization on the surface of the protected object. Luggage polymerization is performed in the form of a rotating drum, the optimal speed for powder coating 30 rpm, the Thickness of the shell is governed by the time of coating. This method is suitable for the encapsulation of any solids (except prone to intense sublimation). Produces the text of poly-n-xylylene vysokokritichnyh polymer, with high orientation and dense packing, provides a conformal coating.

Disadvantages of the proposed method are the complexity and duration of the process, using the method of gas-phase polymerization, which makes the method inapplicable to obtain microcapsules of drugs in polymers protein nature due to the denaturation of proteins at high temperatures.

In Pat. WO/2011/127030 US IPC A61K 8/11; B01J 2/00; B01J 13/06; C11D 3/37; C11D 3/39; C11D 17/00 published on 13.10.2011 proposed several methods for producing microcapsules: interfacial polymerization, thermoanaerobium separation of the phases, spray drying, evaporation of the solvent and other

The disadvantages of the proposed methods is the complexity, duration processes, as well as the use of special equipment (filter (Albet, Dassel, Germany), spray dryer for collecting particles (Spray-4M8 Dryer from ProCepT, Belgium)).

In Pat. WO/2011/104526 GB IPC B01J 13/00; B01J 13/14; C09B 67/00; C09D 11/02 published on 01.09.2011 method for obtaining a dispersion of encapsulated solid particles in a liquid medium, comprising: a) grinding compositions, including solid, liquid medium and a polyurethane dispersant with an acid number of from 0.55 to 3.5 mmol per gram of dispersant, the composition comprises from 5 to 40 parts of the polyurethane dispersant to 100 parts of the solid products in the su; and b) crosslinking the polyurethane dispersant in the presence of solid and liquid medium, so as to encapsulate the solid particles, which polyurethane dispersant contains less than 10% by weight of the recurring elements of polymeric alcohols.

Disadvantages of the proposed method are the complexity and duration of the process of production of microcapsules, and that the encapsulated particles of the proposed method are useful as colorants in inks, especially ink jet printing for the pharmaceutical industry this technique is not applicable.

The closest method is the method proposed in U.S. Pat. 2134967 IPC A01N 53/00, A01N 25/28 published 27.08.1999 Russian Federation (1999). Water is dispersed solution of a mixture of natural lipids and a PYRETHROID insecticide in the weight ratio of 2-4:1 in an organic solvent, which leads to simplification of the method of microencapsulation.

The disadvantage of this method is the dispersion in the aquatic environment, which makes the proposed method applicable to the production of microcapsules of water-soluble drugs in water-soluble polymers.

The technical objective is the simplification and acceleration of the process of obtaining the microcapsules vodorastvorimyh drugs group of cephalosporins in Konakovo gums, reducing losses upon receipt of the microcapsules (increase in mass).

Re the giving of the technical problem is achieved by a method of producing microcapsules drugs group of cephalosporins, related to β-lactam antibiotics, characterized in that as the shell of the microcapsules is Konakova gum, obtaining microcapsules is carried out by physical and chemical deposition method by nerastvorim using two precipitators - carbinol and diethyl ether, the retrieval process is carried out without special equipment.

A distinctive feature of the proposed method is the use as the shell of the microcapsules drug group cephalosporins related to β-lactam antibiotics, Konakovo gums, and obtaining microcapsules physico-chemical deposition method by nerastvorim using two precipitators - carbinol and diethyl ether.

The result of the proposed method are obtaining microcapsules drug group cephalosporins related to β-lactam antibiotics in Konakovo gum at 25°C for 15 minutes. The output of the microcapsules is over 90%.

Required for microencapsulation of Konakova gum was industrial production under the trade name konjac cercon and konjac gum 3600.

EXAMPLE 1. Obtaining microcapsules Ceftriaxone in the konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3

To 6 g of 5% solution of konjac cerocon in diethyl who Fira add 0.01 g of the drug Is (ester of glycerol with one or two molecules of citric acid, and citric acid, as Tihonova may be etherification other glycerides and as hydroxy acid other fatty acids. Free acid groups can be neutralized with sodium as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of Ceftriaxone powder dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the Ceftriaxone independent solid phase very slowly added dropwise 5 ml of carbinol and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.

Obtained 0.35 g of a white powder. The yield was 88%.

EXAMPLE 2. Obtaining microcapsules Cefotaxime in konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3

To 6 g of 5% solution of konjac cerocon in diethyl ether is added 0.01 g of the drug Is as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of the powder Cefotaxime dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the Cefotaxime independent solid phase very slowly added dropwise 5 ml of CT is inola and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.

Received 0.39 g of white powder. The yield was 98%.

EXAMPLE 3. Obtaining microcapsules is anticipated in the konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3

To 6 g of 5% solution of konjac cerocon in diethyl ether is added 0.01 g of the drug Is as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of Cefazolin powder dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the anticipated independent solid phase very slowly added dropwise 5 ml of carbinol and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.

Obtained 0.34 g of a white powder. The yield was 89%.

The obtained microcapsules drug group cephalosporins related to β-lactam antibiotics, in Konakovo gum physico-chemical method for the deposition nerastvorim using carbinol and diethyl ether as precipitators. The process is simple to perform and lasts for 15 minutes, does not require special the real hardware.

Konakova gum is widely used in the pharmaceutical industry drugs for weight loss and regulation chair, as a binder in tablets. In the Russian Federation is permitted in food products according to TI in an amount up to 10 g/kg of product (p SanPiN 2.3.2.1293-03). Technological function: thickener, geleobrazovanie, stabilizer, means for tableting. Composition: neutral polysaccharide glucomannan consists of D-glucose and D-mannose in a ratio of from 1:4 to 2:3. Receive: a three-year, weighing more than a kilogram of root tubers of Amorphophallus plants are cut, dried, milled and sieved flour is subjected to swelling in water, treated with lime milk and filtered. Glucomannan is precipitated from the filtrate with alcohol and dried.

The proposed method is suitable for the pharmaceutical industry due to the minimal loss of speed, ease of acquisition and allocation of microcapsules cephalosporins related to β-lactam antibiotics, in Konakovo gums.

The method of producing microcapsules drugs group of cephalosporins in Konakovo gum in diethyl ether, characterized in that as the shell of the microcapsules is Konakova gum, obtaining microcapsules is carried out by physical and chemical deposition method by nerastvorim using two precipitator is - carbinol and diethyl ether, taken in the ratio 1:3, the retrieval process is carried out at 25°C without special equipment.



 

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