RU2542417C2 - Method for cephalosporin bioencapsulation - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the chemical-pharmaceutical industry, and represents a method for producing drug microcapsules by a non-solvent addition differing by the fact that the drugs represent cephalosporins, while the coating is human serum albumin deposited from an aqueous solution by adding carbinol as the non-solvent and isopropanol at 25°C.

EFFECT: invention provides simplifying and fastening the microencapsulation process, reducing the microencapsulation loss (higher weight yield).

3 ex

Description

The invention relates to the field of bioencapsulation, and in particular to the production of microcapsules of drugs of the cephalosporin group.

Previously known methods for producing microcapsules of drugs. So, in US Pat. RF 2092155, IPC A61K 047/02, A61K 009/16, publ. 10/10/1997 a method of microencapsulation of drugs based on the use of ultraviolet radiation was proposed.

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

In US Pat. RF 2095055, IPC A61K 9/52, A61K 9/16, A61K 9/10, publ. 11/10/1997 a method for producing solid non-porous microspheres is proposed, which includes melting a pharmaceutically inactive carrier substance, dispersing a pharmaceutically active substance in a melt in an inert atmosphere, spraying the resulting dispersion in the form of a fog in a freezing chamber under pressure, in an inert atmosphere, at a temperature from -15 to -50 ° C and the separation of the obtained microspheres into fractions by size. A suspension intended for administration by parenteral injection contains an effective amount of said microspheres distributed in a pharmaceutically acceptable liquid vector, the pharmaceutically active substance of the microsphere being insoluble in said liquid medium.

The disadvantages of the proposed method: obtaining microcapsules by spray cooling, the complexity and duration of the process, the use of special equipment.

In US Pat. RF 2091071, IPC A61K 35/10, publ. 09/27/1997 a method for the preparation of the drug by dispersion in a ball mill with obtaining microcapsules.

The disadvantage of this method is the use of a ball mill and the duration of the process.

In US Pat. RF 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, publ. 01/10/1998 a chewing mask of a taste-masked drug with the properties of controlled release of the drug is proposed that contains microcapsules 100-800 μm in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating that includes a plasticizer that is flexible enough to withstand chewing. The polymer coating is a methacrylic acid based copolymer.

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

In US Pat. RF 2159037, IPC A01N 25/28, A01N 25/30, publ. 11/20/2000 a method for producing microcapsules by a polymerization reaction at the phase boundary containing a solid agrochemical material of 0.1-55 wt.% Suspended in a water-miscible organic liquid, 0.01-10 wt.% Of a non-ionic dispersant active at the interface is proposed phases and not acting as an emulsifier.

The disadvantages of the proposed method: complexity, duration, the use of high shear mixer.

In US Pat. RF 2173140, IPC A61K 009/50, A61K 009/127, publ. 09/10/2001 a method for producing silicon organolipid microcapsules using a rotary-cavitation unit with high shear forces and powerful sonar effects of sound and ultrasonic range for dispersion is proposed.

The disadvantage of this method is the use of special equipment - a rotary-quittance installation, which has an ultrasonic effect, which affects the formation of microcapsules and can cause adverse reactions due to the fact that ultrasound destructively affects polymers of a protein nature, therefore, the proposed method is applicable when work with polymers of synthetic origin.

In US Pat. RF 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, publ. 06/27/2009 a method for producing microcapsules using spray cooling in a Niro spray cooling tower is proposed under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. The microcapsules of the invention have improved stability and provide controlled and / or prolonged release of the active ingredient.

The disadvantages of the proposed method are the duration of the process and the use of special equipment, a set of certain conditions (air temperature at the inlet 10 ° C, air temperature at the outlet 28 ° C, rotation speed of the spray drum 10,000 rpm).

In US Pat. US20110223314, IPC B05D 7/00 20060101 B05D 007/00, B05C 3/02 20060101 B05C 003/02; B05C 11/00 20060101 B05C 011/00; B05D 1/18 20060101 B05D 001/18; B05D 3/02 20060101 B05D 003/02; B05D 3/06 20060101 B05D 003/06 dated 10.03. 2011 US describes a method for producing microcapsules by suspension polymerization, belonging to the group of chemical methods using a new device and ultraviolet radiation.

The disadvantage of this method is the complexity and duration of the process, the use of special equipment, obtaining microcapsules by suspension polymerization, the use of ultraviolet radiation.

The closest method is the method proposed in US Pat. RF 2134967, IPC A01N 53/00, A01N 25/28, publ. 08/27/1999, a solution of a mixture of natural lipids and a pyrethroid insecticide in a weight ratio of 2-4: 1 in an organic solvent is dispersed in water, which simplifies the microencapsulation method.

The disadvantage of this method is dispersion in an aqueous medium, which makes the proposed method inapplicable for producing microcapsules of water-soluble preparations in water-soluble polymers.

The technical task is to simplify and accelerate the process of obtaining microcapsules of water-soluble drugs of the cephalosporin group in human serum albumin, to reduce losses in the production of microcapsules (increase in yield by weight).

The solution to the technical problem is achieved by the method of bioencapsulation of drugs of the cephalosporin group, characterized in that human serum albumin is used as the shell of the microcapsules by their physicochemical precipitation with a non-solvent using two precipitants - carbinol and isopropanol, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of human serum albumin as a shell of microcapsules of drugs of the cephalosporin group.

The result of the proposed method is to obtain microcapsules of drugs of the cephalosporin group in human serum albumin at 25 ° C for 20 minutes. The output of microcapsules is more than 90%.

EXAMPLE 1. Obtaining microcapsules of cefotaxime in albumin using carbinol and isopropanol as precipitants, the ratio of 1: 1

0.130 g of cefotaxime powder and 0.02 g of E472c preparation as a surfactant are added to 13 g of a 1% aqueous solution of albumin. The resulting mixture is placed on a magnetic stirrer and include stirring. After dissolving the components of the reaction mixture until a clear solution forms, very slowly 5 ml of carbinol are added dropwise as the first precipitant, and then 8 ml of isopropanol as the second. The resulting suspension of microcapsules is filtered on a 16-class pore filter, washed with acetone, dried in a desiccator over calcium chloride.

Received 0.240 g of a white with a yellowish tinge of powder. The yield was 92%.

EXAMPLE 2. Obtaining microcapsules of ceftriaxone in albumin using carbinol and isopropanol as precipitants, the ratio of 3: 1

To 6 g of a 2.5% aqueous albumin solution, 0.450 g of ceftriaxone powder and 0.02 g of the preparation E472c as a surfactant are added. The resulting mixture is placed on a magnetic stirrer and include stirring. After dissolving the components of the reaction mixture until a clear solution forms, very slowly 5 ml of carbinol are added dropwise as the first precipitant, and then 15 ml of isopropanol as the second. The resulting suspension of microcapsules is filtered on a 16-class pore filter, washed with acetone, dried in a desiccator over calcium chloride.

Received 0.564 g of a white with a yellowish tinge of powder. The yield was 94%.

EXAMPLE 3. Obtaining microcapsules of cefazolin in albumin using carbinol and isopropanol as precipitants, the ratio of 3: 1

To 6 g of a 2.5% aqueous albumin solution, 0.450 g of cefazolin powder and 0.02 g of the preparation E472c as a surfactant are added. The resulting mixture is placed on a magnetic stirrer and include stirring. After dissolving the components of the reaction mixture until a clear solution forms, very slowly 5 ml of carbinol are added dropwise as the first precipitant, and then 15 ml of isopropanol as the second. The resulting suspension of microcapsules is filtered on a 16-class pore filter, washed with acetone, dried in a desiccator over calcium chloride.

Received 0.564 g of a white with a yellowish tinge of powder. The yield was 94%.

Microcapsules of drugs of the cephalosporin group in human serum albumin were obtained by the physicochemical method of precipitation with a non-solvent using two precipitants - carbinol and isopropanol, which increases the yield and accelerates the microencapsulation process. The process is simple to execute and lasts for 20 minutes, does not require special equipment.

The proposed technique is suitable for the pharmaceutical industry due to minimal losses, speed, ease of preparation and isolation of microcapsules of cephalosporins in human serum albumin.

Claims (1)

A method of producing microcapsules of drugs by the method of precipitation with a non-solvent, characterized in that the drugs used are the cephalosporin group, and the shell is human serum albumin, which is precipitated from an aqueous solution by adding carbinol and isopropanol as a solvent at 25 ° C.