RU2514056C2 - Method for fenbendazole encapsulation - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to drug microencapsulation, particularly for preparing fenbendazole microcapsules. The method is characterised by the fact that a microcapsule coating is carboxymethyl cellulose; fenbendazole dissolved in dioxane or dimethyl sulphoxide (DMSO), or dimethyl formamide (DMFM) is dispersed into the solution of sodium carboxymethyl cellulose in dioxane in the presence of the preparation E472c; further, isopropanol and distilled water are added; the prepared microcapsule suspension is filtered and dried; a process of microcapsules is conducted at 25°C for 20 minutes with no special equipment; with nucleus/polymer ratio making 1:3.

EFFECT: invention provides simplifying and accelerating the process of preparing the fenbendazole microcapsules in carboxymethyl cellulose, reducing losses in preparing the microcapsules (higher weight yield).

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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 Pat.

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 Pat.

The disadvantages of the method are the use of a ball mill and the duration of the process.

Pat. 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19 Russian Federation, published January 10, 1998, proposes a chewable form of the drug with a taste mask that has the properties of a controlled the release of the drug contains microcapsules 100 to 800 microns in diameter 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.

Pat. No. 2173140, IPC A61K 009/50, A61K 009/127 Russian Federation, published September 10, 2001, proposes a method for producing silicon organolipid microcapsules using a rotary-cavitation unit with high shear forces and powerful sonar acoustic and ultrasonic dispersion ranges.

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.

Pat. 2,359,662, IPC A61K 009/56, A61J 003/07, BO 1JO 13/02, A23L 001/00, published June 27, 2009, Russian Federation, provides a method for producing microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: the inlet air temperature is 10 ° C, the outlet air temperature is 28 ° C, the speed of rotation of the spray drum is 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 Pat. 2134967, IPC A01N 53/00, A01N 25/28, published on 08.27.1999, the 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 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 - isopropanol and dioxane, 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 microcapsules, fenbendazole as their core, as well as the use of two precipitants - isopropanol and dioxane.

The result of the proposed method is to obtain 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 dioxane containing the indicated 300 mg of polymer in the presence of 0.01 g of the preparation E472c with stirring 1000 rps. Then pour 2 ml of isopropanol 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 dioxane containing the indicated 300 mg of polymer in the presence of 0.01 g of the preparation E472c with 1000 rpm stirring. Then pour 2 ml of isopropanol 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 dioxane containing the indicated 300 mg of polymer in the presence of 0.01 g of the preparation E472c with 1000 rpm stirring. Then pour 2 ml of isopropanol 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 - isopropanol and dioxane, which helps to increase 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 fenbendazole, characterized in that sodium carboxymethyl cellulose is used as the shell of the microcapsules, while fenbendazole dissolved in dioxane or dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) is dispersed in a solution of sodium carboxymethyl cellulose 72, in the presence of further preparation of carboxymethyl cellulose 72 isopropanol and distilled water are added, the resulting suspension of microcapsules is filtered and dried, the process of obtaining microcapsules is carried out at 25 ° C for 20 minutes without special orudovaniya, wherein the ratio of core / polymer is 1: 3.