RU2614734C2 - Method of producing nanocapsules of rosuvastatin in carrageenan - Google Patents

Abstract

FIELD: nanotechnology.

SUBSTANCE: invention relates to a method of producing nanocapsules of rosuvastatin, characterised by that rosuvastatin is slowly added to a suspension of carrageenan in hexane, in presence of 0.005 g of an E472c preparation with mixing at 1,000 rpm, with weight ratio shell: nucleus 3:1 or 1:5, then adding 5 ml of 1,2-dichloroethane; prepared suspension is filtered and dried at room temperature.

EFFECT: invention provides a simpler and faster process of producing nanocapsules, reduces loss during production (higher weight yield).

1 cl, 3 ex, 1 dwg

Description

The invention relates to the field of nanotechnology and medicine.

Previously known methods for producing microcapsules.

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 sodium chloride microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: air temperature at the inlet 10 ° С, air temperature at the outlet 28 ° С, rotation speed of the spraying drum 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, 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 nanocapsules, reduce losses in obtaining nanocapsules (increase in yield by mass).

The solution to the technical problem is achieved by the method of producing nanocapsules of rosuvostatin, characterized in that carrageenan is used as the shell of the nanocapsules, and rosuvostatin is used as the core when nanocapsules are prepared by non-solvent precipitation using 1,2-dichloroethane as a precipitant.

A distinctive feature of the proposed method is the preparation of nanocapsules by non-solvent precipitation using 1,2-dichloroethane as a precipitant, as well as the use of carrageenan as a particle shell and rosuvostatin as a core.

The result of the proposed method is to obtain nanocapsules of rosuvostatin.

EXAMPLE 1

Obtaining nanocapsules of rosuvostatin in carrageenan, ratio of shell: core 3: 1

0.3 g of rosuvostatin is slowly added to a suspension of carrageenan in hexane containing the specified 0.9 g of polymer in the presence of 0.005 g of the preparation E472c (glycerol ester with one or two molecules of food fatty acids and one or two molecules of citric acid, with citric acid, as tribasic, it can be esterified with other glycerides and as an acid with other fatty acids. Free acid groups can be neutralized with sodium) as a surfactant with stirring at 1000 rpm. Then 3 ml of 1,2-dichloroethane are added. The resulting suspension is filtered and dried at room temperature.

Obtained 1.2 g of nanocapsule powder. The yield was 100%.

EXAMPLE 2

Obtaining nanocapsules of rosuvostatin in carrageenan, ratio shell: core 1: 5

0.5 g of rosuvostatin is slowly added to a suspension of carrageenan in hexane containing the indicated 0.1 g of polymer in the presence of 0.005 g of the preparation E472c with stirring at 1000 rpm. Next, 5 ml of 1,2-dichloroethane are added. The resulting suspension is filtered and dried at room temperature.

Received 0.6 g of nanocapsule powder. The yield was 100%.

EXAMPLE 3

Sizing nanocapsules by NTA.

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

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

Thus, nanocapsules of rosuvostatin with a high yield for 10 min were obtained.

Claims (1)

A method of producing rosuvastatin nanocapsules, characterized in that rosuvastatin is slowly added to a suspension of carrageenan in hexane, in the presence of 0.005 g of the preparation E472c with stirring at 1000 rpm, with a shell: core mass ratio of 3: 1 or 1: 5, then 5 ml of 1 , 2-dichloroethane, the resulting suspension is filtered off and dried at room temperature.

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