Method of production of nanocapsules of albendazole

FIELD: nanotechnology.

SUBSTANCE: according to the invention method, albendazole is added to the suspension of sodium alginate in butanol in the presence of the preparation E472s when stirring at 1000 revolutions per second. The mass ratio of albendazole and sodium alginate is 1:3 or 3:1. Then acetonitrile is added. The resulting suspension of the nanocapsules is filtered, washed, and dried. The process of production of nanocapsules is carried out at 25°C for 20 min.

EFFECT: simplification and acceleration of the process of production of nanocapsules, reduction of losses in their production.

1 dwg, 2 ex

 

The invention relates to the field of nanotechnology in veterinary medicine, in particular nanocapsules of albendazole.

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, proposed a method for microencapsulation of drugs, based on the use of irradiation with ultraviolet rays.

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

In us Pat. 2091071, IPC A61K 35/10, Russian Federation, published 27.09.1997, a method of producing the drug by dispersing in a ball mill to obtain microcapsules.

The disadvantage of this method is the application of the 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 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 fronting�ü chewing. Polymer coating is a copolymer based on methacrylic acid.

Disadvantages of the invention: use of a copolymer based on methacrylic acid, as these polymer coatings can cause cancer; the difficulty of execution; the duration of the process.

In us Pat. 2173140, IPC A61K 009/50, A61K 009/127, Russian Federation, published 10.09.2001, a method of producing kremnijorganicheskih microcapsules using a rotary cavitation equipment with high shear forces and powerful hydroacoustic phenomena sonic and ultrasonic range for dispersion.

The disadvantage of this method is the use of special equipment - rotary-cavitational installation, which has the ultrasonic effect, which influences the formation of the microcapsules and thus may cause adverse reactions due to the fact that ultrasound has a destructive effect on polymers of protein nature, therefore, the proposed method is applicable when working with polymers of synthetic origin.

In us Pat. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00 published 27.06.2009, Russian Federation, proposed a method of producing microcapsules using spray cooling in the spray tower Niro under the following conditions: air temperature at the inlet 10°C, �emperature air at the outlet 28°C, the speed of rotation of the spray drum 10000 rpm/min Microcapsules according to the invention have improved stability and provide adjustable 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, certain set of conditions (the air temperature at the inlet 10°C, the temperature at the outlet 28°C, the speed of rotation of the spray drum 10000 rpm/min).

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

The disadvantage is the dispersion in an aqueous medium, which makes the proposed method applicable for obtaining microcapsules of water-soluble drugs in water-soluble polymers.

The technical objective is the simplification and acceleration of the process of production of microcapsules, reducing loss upon receipt of the microcapsules (increase of the yield by weight).

The solution of a technical problem is achieved by a method of obtaining nanocapsules of albendazole, characterized in that as the shell of the nanocapsules �use sodium alginate when receiving physical-chemical method for the deposition nerastvorim using precipitator-acetonitrile, the receiving process is carried out without special equipment.

A distinctive feature of the proposed method is the use of sodium alginate as the shell of the nanocapsules, albendazole - as their nucleus, and the use of precipitator - acetonitrile.

The result of the proposed method are obtaining nanocapsules of albendazole in sodium alginate at 25°C for 20 minutes. The output of the nanocapsules is over 90%.

EXAMPLE 1. Obtaining nanocapsules of albendazole, the ratio of the core/polymer 1:3

1 g of albendazole added in small portions to a suspension of sodium alginate in butanol containing 3 g of sodium alginate in the presence of 0.01 g of the drug Is (an ester of glycerol with one or two molecules of dietary fatty acids and one or two molecules of citric acid, and citric acid as tribasic can be etherification other glycerides and as oxanilate - other fatty acids. Free acid groups can be neutralized with sodium) under stirring about 1000/sec. Next, pour 6 ml of acetonitrile. The resulting suspension was filtered and dried at room temperature.

Received 4 g of a white powder. The yield was 100%.

EXAMPLE 2. Obtaining nanocapsules of albendazole, the ratio of the core/polymer 3:1

3 g of albendazole in the small portions add in suspended platforms�Oia sodium alginate in butanol, containing 1 g of sodium alginate in the presence of 0.01 g of the drug Is under stirring about 1000/sec. Next, pour 6 ml of acetonitrile. The resulting suspension was filtered and dried at room temperature.

Received 4 g of a white powder. The yield was 100%.

EXAMPLE 3. Determining the size of the nanocapsules NTA method

The measurements were multiparametric analyzer Nanosight nanoparticle LM0 production Nanosight Ltd (UK) in the configuration of the HS-BF (high-sensitivity video camera Andor Luca, a semiconductor laser with a wavelength of 405 nm and a power of 45 mW). The device is based on the method of analysis of the trajectories of the nanoparticles (Nanoparticle Tracking Analysis, NTA), described in ASTM E2834.

The optimal dilution for dilution was chosen as 1:100. For measurements were selected instrument parameters: Camera Level = 16, Detection Threshold = 10 (multi), Min Track Length: Auto, Min Expected Size: Auto. the duration of a single measurement 215s, the use of a syringe pump (Fig. 1).

The obtained nanocapsules of albendazole physico-chemical deposition method by nerastvorim using precipitator - acetonitrile, which increases output and accelerates the process of nanocapsule. The process is simple to perform and lasts for 20 minutes, requires no special equipment.

The proposed method is suitable for the veterinary industry due to the minimal loss of speed, �of rotaty receipt and allocation of microcapsules.

A method of producing nanocapsules of albendazole, characterized by the fact that the albendazole added in small portions to a suspension of sodium alginate in butanol in the presence of the drug Is under stirring about 1000/sec at a weight ratio of albendazole and sodium alginate 1:3 or 3:1, was then added acetonitrile, the process of obtaining nanocapsules was carried out at 25°C for 20 min.



 

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