BG63151B1 - Solid dosage medicamentous forms with avermectin - Google Patents

Abstract

The solid dosage forms based on avermectin have greater stability. They include the customary auxiliary substances and a combination of antioxidants such as ascorbic acid and saccharose or 2,3-dimercaptopropanesulphonate sodium and saccharose in ratio from 1:1 to 1:998. 1 claim

Description

Field of the art

The invention relates to solid dosage forms based on avermectins useful in human and veterinary medicine.

Prior art

The group of avermectin wide-spectrum endectocides, which is a mixture of one to eight components of different biological activity A1a, A2a, A2b, B1a, B1b, B2a, B2b, is known. Highest biological activity has the components B1a and B1b. For better standardization and for the use of the higher active components, the abamectin product has been defined with fixed ratios of components B1a> 80% and B1b <20% (1.2).

Avermectins have limited stability. Their instability is conditioned by both their macromolecular structure and the existence of double bonds. Avermectins are susceptible to the environmental impact of oxidation, reduction (1).

It is known that the predominantly hydrated analogue of abamectin - ivermectin is used in the world practice because of its greater stability due to the reduction in the number of double bonds (1,2,3).

The use of antioxidants used in various avermectin-based compositions is known (4).

A major problem in the placement of both the substance (depending on purification from one to eight components) avermectins and the solid dosage forms containing avermectins is the oxidation (1).

SUMMARY OF THE INVENTION

The invention relates to solid dosage forms based on avermectins that have been stabilized using a combination of antioxidants in a defined ratio.

The resulting solid dosage forms of the present invention may be premixes, tablets, boluses and the like, made up of the classical schemes, including avermectins, excipients such as lactose monohydrate, wheat starch, polyvinylpyrrolodone K25, talc, magnesium stearate, microcrystalline cellulose, corn starch and a combination of antioxidants in a ratio of avermectins to antioxidants from 1: 1 to 1: 998.

The antioxidant content of the dosage forms according to the invention is from 1 to 99.9%.

The combination of antioxidants consists of ascorbic acid and sucrose or of 2,3-dimercaptopropanesulfonate sodium and sucrose in a ratio of 1: 1 to 1: 998.

The advantage of the solid dosage forms according to the invention is that they are of increased stability and resistance to the environmental impact.

Embodiments of the invention

The invention is illustrated by the following non-limiting examples.

Example 1.

Abamectin 0.200 Lactose monohydrate 49,600 Sucrose 50,000 Ascorbic acid 0.200

Example 2.

Abamectin 0.002 Lactose monohydrate 0.160 Wheat starch 0.100 Polyvinylpyrrolidone K25 0.025 Sucrose 0.002 Ascorbic acid 0.002 Talk 0.007 Magnesium stearate 0.002

Example 3,

Avermectins 0.012 Microcrystalline cellulose 1,680 Wheat starch 0.720 Sucrose 0.300 Ascorbic acid 0.030 Polypyrrolidone K25 0.168 Talk 0.060 Magnesium stearate 0.030

Example 4.

Abamectin 0.200 Lactose monohydrate 30,000 Wheat bran 44,600 Polyvinylpyrrolidone K25 '5,000 Sucrose 20,000 Ascorbic acid 0.200

Example 5.

Avermectins 0.100 Sucrose 99,800 Ascorbic acid 0.100

Example 6.

Abamectin 0.002 Lactose monohydrate 0.220 Wheat starch 0.135 Polyvinylpyrrolidone K25 0.030 Sucrose 0.002 2,3-dimercaptopropanesulfonate sodium 0.002 Talk 0.008 Magnesium stearate 0.003

D)

Example 7

Abamectin 0.200 Cornstarch • 49,600 Sucrose 40,000 2, 3-dimercaptopropanesulfonate sodium 0.200

Example 8.

Abamectin 0.100 Sucrose 99,800 2, 3-dimercaptopropanesulfonate sodium 0.100

of preparations containing abamectin with and without a combination of antioxidants (sucrose + vitamin C), there is a significant increase in the shelf-life of the combination of antioxidants.

Application of the invention

Studies have been conducted to demonstrate the stability of the preparation in order to improve its use.

In parallel studies stability-

Conditions under which No combination With a combination has been investigated FROM FROM stability antioxidants, antioxidants, If If m m Accelerated aging (40 ° C) Initial analysis 2.10 2.20 6 months 2.02 2.14 12 months 1.90 2.11 18 months 1.83 2.05 24 months 1.68 2.10 36 months 1.47 1.95

i

In parallel studies, the stability of preparations containing abamectin with and without a combination of antioxidants such as sucrose and sodium 2,3-dimercaptopropanesulfonate revealed a significant increase in shelf life in the combination of antioxidants.

Conditions for WHICH has been investigated stability No combination from antioxidants, A7 (md) With a combination from antioxidants, AU (md) Accelerated aging (40 ° C) Initial analysis 2.10 2.20 6 months 2.02 2.10 12 months 1.90 2.01 18 months 1.83 2.05 24 months 1,68 * 2.00 36 months 1,47 * 1.98

* amount of the active substance below the lower limit of quamate content of abamectin in a dosage form

Claims (4)

1. Solid avermectin dosage forms containing conventional excipients and antioxidants, characterized in that the combination of antioxidants is ascorbic acid and sucrose or 2,3-dimercaptopropanesulfonate sodium and sucrose in a ratio of 1: 1 to 1: 998. Literature 1. Satien \ US. (ed.). 2. Megs 1pdech. 3. \ Uaigeg S., (ed), Sörggeppshtt oa Oahah 5eye1z oa Ue1eppagu Rhodis1z, 1996-1997, OaShrebagt RüPayop Id., Joopdop, 1996. 4. EP 697814.