RU2545742C2 - Lactobifadol encapsulation method - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to microencapsulation of lactobifadol. The method of encapsulating lactobifadol in a shell made of sodium carboxymethyl cellulose is carried out as follows. Lactobifadol is dissolved in dioxane or dimethyl sulphoxide or dimethyl formamide, followed by addition of the obtained lactobifadol solution to a solution of sodium carboxymethyl cellulose in sulphuric ether in the presence of an E472c preparation while stirring at 1000 rps. The lactobifadol and sodium carboxymethyl cellulose are taken in weight ratio of 1:3. Distilled water is then added in amount of 1 ml and the obtained suspension is filtered and dried. The process of producing lactobifadol microcapsules is carried out at 25°C for 20 min.

EFFECT: method speeds up the microencapsulation process and reduces losses (high mass output).

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Description

The invention relates to the field of encapsulation, in particular the production of microcapsules of lactobifadol.

Previously known methods for producing microcapsules of drugs. So, in US Pat. 2092155, IPC A61K 047/02, A61K 009/16, published 10.10.1997, Russian Federation, a method of microencapsulation of drugs based on the use of ultraviolet radiation is 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. 2091071, IPC A61K 35/10, Russian Federation, published 09/27/1997, a method for producing the preparation by dispersion in a ball mill to obtain microcapsules is proposed.

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

In US Pat. 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, Russian Federation, published 01/10/1998, a chewing form of the drug with a taste masking having the properties of a controlled release of the drug The preparation contains microcapsules with a size of 100-800 microns in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating, including a plasticizer, 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. 2173140, IPC A61K 009/50, A61K 009/127, Russian Federation, published September 10, 2001. A method for producing silicon organolipid microcapsules using a rotary-cavitation unit with high shear forces and powerful sonar acoustic and ultrasonic dispersion ranges is proposed.

The disadvantage of this method is the use of special equipment - a rotary cavitation unit, 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. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, published June 27, 2009, Russian Federation, a method for producing microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: air temperature inlet 10 ° C; outlet air temperature 28 ° C; spray drum rotation speed 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).

The closest method is the method proposed in US Pat. 2134967, IPC A01N 53/00, A01N 25/28, published on 08.27.1999, Russian Federation (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, reducing losses when receiving microcapsules (increase in yield by mass).

The solution to the technical problem is achieved by the method of encapsulation of lactobifadol, characterized in that sodium carboxymethyl cellulose is used as the shell of the microcapsules when they are obtained by the physicochemical method of precipitation with a non-solvent using sulfur ether as a precipitant, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of sodium carboxymethyl cellulose as a shell of lactobifadol microcapsules as their core, as well as the use of sulfuric ether as a precipitant.

The result of the proposed method is to obtain lactobifadol microcapsules in sodium carboxymethyl cellulose at 25 ° C for 20 minutes. The output of microcapsules is more than 90%.

EXAMPLE 1. Obtaining microcapsules of lactobifadol with the dissolution of the drug in dioxane, the ratio of core / polymer 1: 3

100 mg of lactobifadol is dissolved in 1 ml of dioxane and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in 5 ml of sulfuric ether containing 300 mg of this polymer in the presence of 0.01 g of the preparation E472c (glycerol ester with one or two food-grade fatty acids and one two molecules of citric acid, moreover, citric acid as a tribasic acid can be esterified with other glycerides and an oxo acid with other fatty acids. Free acid groups can be neutralized with sodium) with stirring 100 0 rpm Then pour 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.356 g of a white powder. The yield was 89%.

EXAMPLE 2. Obtaining microcapsules of lactobifadol with the dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 3

100 mg of lactobifadol is dissolved in 1 ml of DMSO and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in 5 ml of sulfuric ether containing 300 mg of the indicated polymer in the presence of 0.01 g of the preparation Е472с with 1000 rpm stirring. Then pour 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.356 g of a white powder. The yield was 89%.

EXAMPLE 3. Obtaining microcapsules of lactobifadol with the dissolution of the drug in dimethylformamide (DMF), the ratio of core / polymer 1: 3

100 mg of lactobifadol is dissolved in 1 ml of DMF and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in 5 ml of sulfuric ether containing 300 mg of this polymer in the presence of 0.01 g of the preparation E472c with stirring 1000 r / sec. Then pour 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.356 g of a white powder. The yield was 89%.

Microcapsules of lactobifadol were obtained by the physicochemical precipitation method with a non-solvent using sulfur ether as a precipitant, 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 veterinary industry due to minimal losses, speed, ease of obtaining and isolation of microcapsules.

Claims (1)

A method of encapsulating lactobifadol in a shell of sodium carboxymethyl cellulose, characterized in that lactobifadol is dissolved in dioxane or dimethyl sulfoxide or dimethylformamide, add the resulting solution of lactobifadol to a solution of sodium carboxymethyl cellulose in sulfuric ether in the presence of E472 sodium carboxymethyl cellulose and stirring with stirring take in a mass ratio of 1: 3, then add 1 ml of distilled water, the resulting suspension is filtered and dried, while the process obtaining microcapsules of lactobifadol is carried out at 25 ^about C for 20 minutes.