SU1113123A1 - Method of preparing water solution of vitamin k1 - Google Patents

Abstract

A method for producing a aqueous solution of vitamin K using a mixture of vitamin K with tween 80 and water in a stream of inert gas when heated, characterized in that, in order to maintain the stability of the target product, tween 80 is mixed with water to a final 5575% concentration, heated vitamin K is added, and homogenized by vibrating.

Description

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OE 1 The invention relates to a chemical-pharmaceutical industry, in particular to the preparation of an aqueous solution of vitamin K. A method is known for preparing an aqueous solution of vitamin K by adding to the heated mixture a vitamin with surface-active substances, dropwise with continuous stirring. Oxyethylated castor oil and polyoxyethylenesorbitan (.11 The disadvantage of the known method is a high content of supercurrent} u-act 11P}) of mixed substances in a mixture of from 6 to 25 parts by weight. on 1 weight, part of vitamin K, (on average, 15-20 parts by weight per 1 part of vitamin K /,), which leads to an increase in the toxicity of the dosage form. A method is known for producing an aqueous solution of vitamin K, which consists in adding dropwise water with a temperature of 60-70 ° C to a mixture of vitamin K with 4-5 and a multiple of 80 tween and an amount of vitamin K that is heated to 4050 °. With stirring. The mixture is carried out under illumination with red light under the protection of nitrogen C21. The disadvantages of this method are the need to add the second auxiliary substance, propylene glycol, to the dosage form, the need for continuous heating of the mixture containing the thermostable substance polyoxyethylene sorbitan (Tween 80). Thus, with a more or less prolonged heating above 40 ° C, Tween 80 decomposes, accompanied by the release of chemically active peroxides. The presence of peroxides in the mixture leads to inactivation of vitamin K ;, mixed with secret 80, and a decrease in the transparency of the solution (deterioration of the tween 80 colloidal characteristics). The introduction of antioxidants butyloxytoluene and butyloxyanisole leads to an increase in yield, but the discrepancy in quantitative content from 80 to 100% from experience to experience continues to occur. In addition, vitamin K is decomposed by light. Following the process, i.e. mixing the dropwise added water with vitamin Kf 31 and tween requires visual monitoring and, therefore, sufficient illumination of the mixture (regulation of the water supply rate, agitator speed), which also adversely affects the quality of the final product, resulting in loss of vitamin TO,. Obtaining vitamin K by this method is almost impossible. The viscosity of a mixture of vitamin K. and tween 80 increases dramatically with the addition of water. A disruption to the operation of the mechanical mixer is created. Conducting experiments in the absence of 1,2-propanediol leads to the need to raise the temperature of the mixture to 50 ° C, lengthen the heating time and, as a result, large losses of vitamin K at the production stages and high turbidity of the resulting final solution of vitamin K. It is impossible to increase the power of the mechanical mixer due to low surface tension, high mass viscosity and the possibility of foaming. Stirring the thick mass by shaking is technically difficult. Control in this case is difficult. It is necessary to thermostat the mass during shaking, to shake in inert gas. All this does not allow us to recommend mechanical mixing for an industrial method of production. The drug obtained in a known manner is not stable enough. The purpose of the invention is to increase the stability of the target product. This goal is achieved by the fact that according to the method of obtaining an aqueous solution of vitamin K "using a mixture of vitamin K, | with tween 80 and water in a stream of inert gas with an; After mixing, tween 80 is mixed with water to a final concentration of 55-75% concentration / heated, vitamin K is added and homogenized by vibration mixing. Example 1. C4g tween 80 add 0.05 g of butyloxyanisole (preservative) and 1.33 g of double distilled water to obtain a 75% aqueous solution. The solution is heated until 1 g of vitamin K is added, homogenized by vibrating at 50 Hz for 1 min, and diluted with double distilled water,

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to which was added 0.7 g of potassium chloride to a volume of 100 ml. All operations are carried out under nitrogen protection. Next, the solution is filtered and poured into ampoules. The ampoules are sealed and subjected to fractional sterilization of the pH of an ampulized solution of 6-7. Turbidity, determined on the FEK H57 (filter 11) in a 5 dpina cuvette (control-water) is no more than J. The content of vitamin K, determined according to the CLIA XIX pharmacopoeia, is not less than 95% of the theoretical.

Example 2: Tween 80 CUg is added with 0.05 g of butyloxyanisole (preservative) and a ml of double distilled water to obtain a 65% solution. 1 g of vitamin K is added, homogenized by vibration mixing for 0.5 minutes, diluted with double distilled water, to which 0.7 g of potassium chloride is added to a volume of 100 ml. All operations are carried out under nitrogen protection. Next, the solution is filtered and poured into ampoules. The ampoules are sealed and subjected to fractional sterilization of the pH of the ampulirovanny solution 6-7. Turbidity, determined on FEK-N57 (light filter No. 11) in a cuvette 5 cm long (control-water), is no more than D. Vitamin K content, determined according to the United States Pharmacopoeia XIX edition, not less than 95% of the theoretical one.

Example 3. K4g Tween 80 was added 3.2 ml of double distilled water to obtain 55%

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solution. 1 g of vitamin K is added, 0.5 g of phenol is added as a preservative, homogenized for 1 minute at 50 ° C, and diluted with double distilled water, to which was added 0.7 g of potassium chloride, to a volume of 100 ml. All operations are carried out under nitrogen protection. Next, the solution is filtered and poured into ampoules. The pH of the resulting solution should be 6-7. If necessary, 0.1 g of sodium hydroxide is added to the solution to bring the pH to the specified range. Turbidity no more than J (FEC-H57, filter No. 11, cuvette 5 cm, control water). The vitamin content is not less than 95% of the theoretical. The stability of the aqueous solution of vitamin K obtained by the proposed method is maintained for 1.5 years. While by a known method, the stability is reduced within 6 months.

The proposed method for the preparation of clear solutions of vitamin K,

5 provides, in comparison with the known, the following advantages: the possibility of obtaining transparent solutions of vitamin K with a high yield of vitamin K in arbitrarily large quantities, which is especially important for the development of an industrial method of production; possibility of automatic control over the process at all stages. The proposed method can be used to obtain aqueous solutions of other liquid-soluble vitamins and the like.

Claims (1)

METHOD FOR PRODUCING A WATER SOLUTION OF VITAMIN K, using a mixture of vitamin K _t with tween 80 and water in an inert gas stream during heating, characterized in that, in order to increase the stability of the target product, tween 80 is mixed with water to a final 5575% concentration, heated, add vitamin K „and homogenized by vibration mixing. 1 I I