Pharmaceutical-grade povidone K30 is used as a binder and co-solvent

Pharmaceutical-grade povidone K30 is a non-ionic polymer compound characterized by N-vinylamide polymers and the most studied and widely studied fine chemicals
.
It has developed into three categories of non-ionic, cationic and anionic, three specifications of industrial grade, pharmaceutical grade and food grade, and a series of homopolymers, copolymers and crosslinked polymers with a relative molecular weight from thousands to more than one million, and has been widely used
in its excellent performance.
Povidone is widely used in pharmaceutical applications, mainly in
solid preparations.
In tablets, povidone solutions act as binders
in wet granulation.
Povidone powder can also be mixed directly into other powders in a dry state, and then granulated
by adding water, alcohol or aqueous alcohol solution.
In oral or parenteral administration, povidone acts as a solubilizer to accelerate the dissolution of poorly soluble drugs from solid preparations
.
Povidone solution can also be used as a coating material
.
In addition, povidone also acts as a suspension, stabilizer, or tackifier in some topical and oral suspensions and solutions
.
Many poorly soluble drugs increase solubility when mixed with povidone
.
【Check】Acidity take 1.
0g of this product, add 20ml of water to dissolve, check according to law (General 0631), the pH value should be 3.
0~5.
0
.
Clarity and color of the solution take 1.
0g of this product, add 20ml of water to dissolve, the solution should be clear and colorless, such as turbidity, compared with No.
1 turbidity standard solution (General 0902), not more concentrated; such as color development, compared with yellow No.
1 or brown-red No.
2 standard colorimetric solution (General 0901 first method), not deeper
。 K value take 1.
00g of this product (calculated according to anhydrous), weigh it accurately, put it in a 100ml measuring flask, add an appropriate amount of water to dissolve, and dilute to the scale, put it in a constant temperature water bath at 25 °C± 0.
2 °C for 1 hour, check according to law (General 0633 second method), measure the relative viscosity ηr, calculate the K value according to the formula, it should be 27.
0~32.
0
.
where W is the weight of the test product (calculated as anhydrous), g
.
Aldehyde take 1.
0g of this product, put it in a 100ml measuring flask, add phosphate buffer (take 1.
74g of potassium dihydrogen phosphate, add 80ml of water to dissolve, adjust the pH value to 9.
0 with 1mol/L potassium hydroxide solution, and then dilute it to 100ml with water, that is) dissolve and dilute to the scale, shake well, plug it, and place it in a constant temperature water bath at 60 °C for 1 hour, then let it cool as a test solution
。 In addition, take 0.
140g of acetaldehyde ammonia trimer, put it in a 200ml measuring flask, dissolve it with water and dilute it to the scale, shake well, take 1ml accurately, put it in a 100ml measuring flask, dilute it to the scale with phosphate buffer, shake well, and use it as a reference solution
。 Take 0.
5ml of the test solution accurately, put it in a cuvette, add 2.
5ml of phosphate buffer in turn, nicotinamide adenine dinucleotide solution (take an appropriate amount of β-nicotinamide adenine dinucleotide, put it in a glass bottle, add phosphate buffer to dissolve and dilute to make a solution containing 4mg per 1ml, stored at 4 °C, stable within 4 weeks) 0.
2ml, capped, mixed, placed in a water bath at 22 °C± 2 °C for 2~3 minutes, with water as a reference, according to ultraviolet-visible spectrophotometry (General 0401) , to determine the absorbance at a wavelength of 340 nm; Then add aldehyde dehydrogenase solution to the same cuvette (take an appropriate amount of low-pressure lyophilized powder aldehyde dehydrogenase, put it in a glass bottle, add water to dissolve and dilute to make a solution containing 7U per 1ml, stored at 4 °C, stable within 8 hours) 0.
05ml, capped, mixed, placed in a water bath at 22 °C ± 2C for 5 minutes, with water as a reference, absorbance
was measured at a wavelength of 340nm.
Take another blank solution (water) and a reference solution for the same operation
.
The aldehyde content is calculated by the following formula, calculated by acetaldehyde, and shall not exceed 0.
05%.

where At1 is the absorbance of the test solution before adding aldehyde dehydrogenase; AT2 is the absorbance of the test solution after adding aldehyde dehydrogenase; As1 is the absorbance of the reference solution before adding aldehyde dehydrogenase; As2 is the absorbance of the reference solution after adding aldehyde dehydrogenase; AB1 is the absorbance of the blank solution before adding aldehyde dehydrogenase; AB2 is the absorbance of the blank solution after adding aldehyde dehydrogenase; C is the concentration of the reference solution, mg/ml (the coefficient of acetaldehyde ammonia trimer converted to acetaldehyde is 0.
72); m is the sampling amount (calculated as anhydrous), g
.
N-vinylpyrrolidone take about 0.
25g of this product, weigh it accurately, put it in a 10ml measuring flask, add mobile phase to dissolve and dilute to the scale, shake well, and use it as a test solution
.
In addition, take an appropriate amount of N-vinylpyrrolidone reference substance, weigh it accurately, add methanol to dissolve and dilute to make a solution containing about 5μg per 1ml, take 5ml accurately, put it in a 100ml measuring flask, dilute it to the scale with mobile phase, shake well, and use it as a reference solution
.
In addition, take an appropriate amount of N-vinylpyrrolidone reference substance and vinyl acetate, add an appropriate amount of methanol to dissolve, dilute it with mobile phase and prepare a solution containing 1μg of N-vinylpyrrolidone and 50μg of vinyl acetate per 1ml as a system suitability test solution
.
According to high performance liquid chromatography (General 0512), octadecylsilane bonded silica gel was used as the filler, acetonitrile-water (10:90) was used as the mobile phase, and the detection wavelength was 235nm
.
Take 20μl of the system suitability test solution and inject it into the liquid chromatograph, the resolution of N-vinylpyrrolidone peak and vinyl acetate peak should be greater than 6.
0, and the resolution of N-vinylpyrrolidone and adjacent chromatographic peaks in the test solution should meet the requirements
.
Take 20μl of the test solution and 20μl of the reference solution with precision, inject them into the liquid chromatograph respectively, record the chromatogram, and calculate the peak area according to the external standard method, not exceeding 0.
001%.

2-Pyrrolidone take an appropriate amount of this product, weigh it accurately, add water to dissolve and dilute into a solution containing 5mg per lml as a test solution
.
Take an appropriate amount of 2-pyrrolidone reference substance, weigh it accurately, add water to dissolve and dilute to make a solution containing 0.
1mg per 1ml as a reference solution
.
According to high performance liquid chromatography (General 0512), octadecylsilane bonded silica gel was used as filler, water-acetonitrile-methanol was used as mobile phase (90:5:5), and the detection wavelength was 205nm
.
Take 20μl of the reference solution accurately, inject it into the liquid chromatograph, inject it 6 times, and the relative standard deviation of the peak area shall not exceed 2.
0%.

Take 20μl of the reference solution and 20μl of the test solution with precision, inject it into the liquid chromatograph respectively, record the chromatogram, and calculate the peak area according to the external standard method, which shall not exceed 2.
0%.

formic acid take 0.
50g of this product, weigh it accurately, put it in a 100ml measuring flask, add mobile phase to dissolve and dilute to the scale, shake well, and use it as a test solution
.
take an appropriate amount of formic acid reference substance, weigh it accurately, add mobile phase to dissolve and dilute to make a solution containing 25μg per 1ml as a reference solution
.
According to high performance liquid chromatography (General 0512), octadecylsilane bonded silica gel was used as the filler, 0.
01mol/L potassium dihydrogen phosphate solution-acetonitrile (95:5) (pH value was adjusted to 3.
0 with phosphoric acid) as the mobile phase, and the detection wavelength was 210nm
.
The resolution between formic acid and adjacent peaks in the test solution should meet the requirements
.
Take 20μl of the reference solution and 20μl of the test solution with precision, inject it into the liquid chromatograph respectively, record the chromatogram, and calculate the peak area according to the external standard method, not more than 0.
5%.

Peroxide take 4.
0g of this product (calculated as anhydrous), put it in a 100ml measuring flask, add water to dissolve and dilute to the scale, shake well, and use it as a stock solution
.
Take 25ml accurately, 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 the stock solution accurately, add 2.
0ml of 13% sulfuric acid solution, shake well, place for 30 minutes, as a blank solution, according to ultraviolet-visible spectrophotometry (General 0401), the absorbance is measured at a wavelength of 405nm, not more than 0.
35 (equivalent to 0.
04% H2O2).

Hydrazine take 2.
5g of this product, precision weighing, placed in a 50ml centrifuge tube, the specific shift value (Rf) of azine is about 0.
3, if the test solution shows fluorescent spots corresponding to the reference solution, its fluorescence intensity shall not be stronger (0.
0001%)
than the spots of the reference solution.
water take this product, according to the moisture determination method (General 0832), the moisture content shall not exceed 5.
0%.

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

Heavy metals Take the residue left under the item of ignition residue and inspect it according to law (General Principles 0821 Second Law), and the content of heavy metals shall not exceed 10
parts per million.
nitrogen content take about 0.
1g of this product, weigh it accurately, put it in a Kjeldahl flask, add 10g of potassium sulfate and 0.
5g of copper sulfate in turn, slowly add 20ml of sulfuric acid along the wall of the bottle, put a small funnel at the mouth of the Kjeldahl nitrogen flask, slowly heat it with a direct fire, the solution is clear green, continue to heat for 30 minutes, and let it cool
.
Transfer to a 100ml measuring flask, dilute to the scale with water and shake well
.
Precision aspiration of 10ml, according to the nitrogen determination method (General 0704 second method or third method), the distillate with sulfuric acid titration solution (0.
005mol/L) and the results of the titration were corrected
with a blank test.
According to the calculation of anhydrous, the nitrogen content should be 11.
5%~12.
8%.