Medical grade copovidone experiment application research and development test

Medical grade copovidone experiment declaration research and development of copovidone Gongjuweitong Copovidone This product is 1-vinyl-2-pyrrolidone and vinyl acetate copolymerization in a mass ratio of 3:2
.

According to the calculation of anhydrous, the nitrogen content (N) should be 7.
0%~8.
0%; Vinyl acetate containing copolymer (C4H6O2) should be 35.
3% to 41.
4%.


【Properties】This product is white or yellow-white powder or flake solid
.

This product is soluble
in water, ethanol or dichloromethane.

【Identification】(1) Take 5ml of this aqueous solution (l→50) and add 1 to 2 drops of iodine test solution, that is, brownish red
.

(2) Take 0.
1g of this product, add hydroxylamine hydrochloride solution (take hydroxylamine hydrochloride 0.
7g, add methanol to dissolve and dilute to 10ml, add 1mol/L sodium hydroxide solution 20ml, shake well, filter if necessary) 5ml, heat and boil for 2 minutes, cool to room temperature, take 50μl on filter paper, add ferric chloride solution (10.
5% ferric chloride solution mixed with hydrochloric acid and other volumes) 0.
1ml, that is, purple
.

(3) The infrared light absorption pattern of this product should be consistent with the map of the control product (General Rule 0402
).

【Check】 The clarity and color of the solution After taking 1.
0g of this product and adding 10ml of water to dissolve, the solution should be clear and colorless, if it is cloudy, it shall not be more concentrated compared with the No.
3 turbidity standard (General 0902); if the color is developed, it shall not be darker
compared with the yellow No.
2 or brownish red No.
3 standard colorimetric liquid (General Rule 0901).

K value Take 1.
00g of this product (calculated according to anhydrous), precision weighing, placed in a 100ml measuring bottle, add water to dissolve, and dilute to the scale, shake well, after placing in a constant temperature water bath of 25 ° C ± 0.
2 ° C for 1 hour, check according to law (general rule 0633 second method), measure the relative viscosity ηr, calculate the K value according to the formula, should be 90.
0% ~ 110.
0%
of the marked amount.

Aldehyde Take 1.
0g of this product, weigh it precisely, place it in a 100ml measuring flask, add phosphate buffer (take potassium dihydrogen phosphate 1.
74g, add water 80ml to dissolve, adjust the pH to 9.
0 with 1mol/L potassium hydroxide solution, and then add water to dilute to 100ml, that is, to obtain) dissolve and dilute to the scale, shake well, dense plug, place in a 60 °C constant temperature water bath for 1 hour, let it cool, as a test solution
.

Take another acetaldehyde ammonia trimer 0.
140g, put in a 200ml measuring flask, add water to dissolve and dilute to the scale, shake well, take 1ml with precision, put in a 100ml measuring flask, dilute with phosphate buffer to the scale, shake well, as a control solution
.

Take 0.
5ml of the sample solution in precise amount, put it in a cuvette dish, add phosphate buffer 2.
5ml in turn, niacinamide adenine dinucleotide solution (take β-nicotinamide adenine dinucleotide appropriate amount, add phosphate buffer to dissolve and dilute to make a solution containing 4mg per 1ml, store at 4 °C, stable within 4 weeks) 0.
2ml, cap, mix, place in a water bath at 22 °C + 2 °C for 2 to 3 minutes, with water as a reference, According to ultraviolet-visible spectrophotometry (General 0401), the absorbance is determined at a wavelength of 340 nm; Then add aldehyde dehydrogenase solution (take a low-pressure lyophilized powder aldehyde dehydrogenase appropriate amount, dissolve and dilute in water to make a solution containing 7U per 1 ml, store at 4 °C, stable within 8 hours) 0.
05ml, cap, mix, place in a water bath at 22 °C ± 2 °C for 5 minutes, take water as a reference, and determine the absorbance
at a wavelength of 340 nm.

Take another blank solution (water) and control solution for the same method of operation
.

The aldehyde content calculated by the following formula, measured by acetaldehyde, shall not exceed 0.
05%.


The monomer (N-vinylpyrrolidone, vinyl acetate and 2-pyrrolidone) takes about 0.
5g of this product, weighs it precisely, places it in a 10ml measuring flask, adds 2ml of methanol to dissolve, dilutes with water to the scale, shakes well, and serves as a test solution
.

Take N- vinyl pyrrolidone, vinyl acetate and 2-pyrrolidone control in an appropriate amount, precise weighing, dissolved and diluted with methanol to make a solution containing about 10μg of N-vinylpyrrolidone and vinyl acetate each 10μg, containing 2-pyrrolidone 5.
0mg, take 5ml with precision, put in a 100ml measuring flask, add mobile phase A dilution to the scale, shake well, as a control solution
.

According to the high performance liquid chromatography (General Rule 0512), the octadecyl silane bonded silica gel is used as the filler (it is recommended to use a 250mm column, using octadecyl silane bonded silica gel as the protective column of the filler), with aqueous - acetonitrile - methanol (90:5:5) as the mobile phase A, and aqueous - acetonitrile - methanol (50:45:5) as the mobile phase B; Column temperature is 30 °C; Gradient elution is performed according to the following table; The detection wavelength of 2-pyrrolidone and vinyl acetate is 205 nm, and the detection wavelength of N-vinylpyrrolidone is 235 nm
.

Take 20 μl of the control solution and inject it into a liquid chromatograph, and the resolution between the 2-pyrrolidone peak, the N-vinylpyrrolidone peak and the vinyl acetate peak should all be greater than 2.
0
.

Take 20 μl of the test solution and the control solution with precision, inject them into the liquid chromatograph respectively, record the chromatography, and calculate the peak area according to the external standard method, N-vinylpyrrolidone, vinyl acetate shall not exceed 0.
001%, and 2-pyrrolidone shall not exceed 0.
5%.


Peroxide Take 4.
0g of this product (calculated according to anhydrous), weigh precisely, place in a 100ml measuring bottle, add water to dissolve and dilute to the scale, shake well, as a storage liquid
.

Take 25ml with precision, add 2.
0ml of titanium trichloride-sulfuric acid solution, shake well, and place for 30 minutes as a test solution
.

In addition, take 25ml of storage solution with precision, add 2.
0ml of 13% sulfuric acid solution, shake well, place for 30 minutes, as a blank solution, according to ultraviolet-visible spectrophotometry (General Rule 0401), determine the absorbance at a wavelength of 405 nm, not more than 0.
35 (equivalent to 0.
04% H2O2).


Hydrazine take 2.
5g of this product, weigh precisely, place in a 50ml centrifuge tube, add 25ml of water to dissolve, add 5% methanol solution 0.
5ml, shake well, heat in a water bath at 60 ° C for 15 minutes, let cool, add xylene 2.
0ml, Miston, shake vigorously for 2 minutes, centrifuge, take the supernatant of the xylene layer as the test solution
.

Another precise weighing of the appropriate amount of acazine control, dissolved and diluted with xylene to make a solution containing 9 μg per lml as a control solution
.

According to the thin layer chromatography (General Rule 0502) test, precision aspirate 10 μl of each of the above two solutions, respectively, dotted on the same dimethylsilylated silica gel thin layer plate, methanol - water (80:20) as the unfolding agent, unfolded, removed, dried, placed under an ultraviolet lamp (365nm) to examine, the test solution such as the corresponding fluorescent spots with the control solution, its fluorescence intensity and the specks of the control solution, shall not be stronger (0.
0001
。
Loss on drying Take this product, dry at 105 ° C to constant weight (general rule 0831), the weight reduction shall not exceed 5.
0%.


Blazing residue Take 1.
0g of this product, check according to law (General Rule 0841), and the residual residue shall not exceed 0.
1%.


Heavy metals: Take the residues left under the incineration residue and inspect them according to law (General Rule 0821 Second Law), and the heavy metals shall not exceed 20
parts per million.

【Content determination】Copolymer vinyl acetate Take this product, determine the saponification value according to law (General Rule 0713), and calculate the content
of vinyl acetate polymerized in the sample according to the formula.

Nitrogen content Take about 0.
35g of this product, weigh it precisely, determine it according to the nitrogen determination method (general rule 0704 first method or third method), calculate, that is, obtained
.

【Category】Pharmaceutical excipients, film formers and adhesives, etc
.

【Storage】Sealed and preserved
.