RU2544165C2 - Method of fenbendazole encapsulation - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the chemical-pharmaceutical industry and represents a method of medication encapsulation by a method of precipitation with a non-solvent, characterised by the fact that as the medication used is fenbendazole and as an envelope sodium carboxymethylcellulose, which is precipitated from a solution in cyclohexanol by the addition of ethanol as the non-solvent and water at 25°C.

EFFECT: invention ensures the simplification and acceleration of the process of obtaining microcapsules, reduction of loss in obtaining the microcapsules (increase of output by weight).

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Description

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

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 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 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).

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, reducing losses when receiving microcapsules (increase in yield by mass).

The solution to the technical problem is achieved by the method of encapsulation of fenbendazole, characterized in that sodium carboxymethyl cellulose is used as the shell of the microcapsules by their physicochemical precipitation with a non-solvent using two precipitators - ethanol and cyclohexanol, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of sodium carboxymethyl cellulose as the shell of microcapsules, fenbendazole as their core, as well as the use of two precipitants - ethanol and cyclohexanol.

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

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

100 mg of fenbendazole is dissolved in 1 ml of dioxane and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in cyclohexanol containing 300 mg of the indicated polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 rpm. Then pour 2 ml of ethanol and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.396 g of a white with a yellowish tinge of powder. The yield was 99%.

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

100 mg of fenbendazole is dissolved in 1 ml of DMSO and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in cyclohexanol containing 300 mg of the indicated polymer in the presence of 0.01 g of the preparation E472c with stirring 1000 rps. Then pour 2 ml of ethanol and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.396 g of a white with a yellowish tinge of powder. The yield was 99%.

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

100 mg of fenbendazole is dissolved in 1 ml of DMF and the resulting mixture is dispersed in a solution of sodium carboxymethyl cellulose in cyclohexanol containing 300 mg of the indicated polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 rpm. Then pour 2 ml of ethanol and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.396 g of a white with a yellowish tinge of powder. The yield was 99%.

Fenbendazole microcapsules were obtained by the physicochemical non-solvent precipitation method using two precipitants - ethanol and cyclohexanol, 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 a drug with a non-solvent precipitation method, characterized in that fenbendazole is used as a drug, and sodium carboxymethyl cellulose is used as a coating, which is precipitated from a solution in cyclohexanol by adding ethanol and water at 25 ° C as a non-solvent.