Povidone

(Ph Eur monograph 0685)

 

(C6H9NO)n              (111.1)n      9003-39-8

 

Ph Eur


 

 

DEFINITION

 

a-Hydro-w-hydropoly[1-(2-oxopyrrolidin-1-yl)ethylene]. It consists of linear polymers of 1-ethenylpyrrolidin-2-one.

 

Content

 

11.5 per cent to 12.8 per cent of nitrogen (N; Ar 14.01) (anhydrous substance).

 

The different types of povidone are characterised by their viscosity in solution, expressed as a K-value.

 

The K-value of povidone having a stated K-value of 15 or less is 85.0 per cent to 115.0 per cent of the stated value.

 

The K-value of povidone having a stated K-value or a stated K-value range with an average of more than 15 is 90.0 per cent to 108.0 per cent of the stated value or of the average of the stated range.

 

CHARACTERS

 

Appearance

 

White or yellowish-white powder or flakes, hygroscopic.

 

Solubility

 

Freely soluble in water, in alcohol and in methanol, slightly soluble in acetone.

 

IDENTIFICATION

 

First identification

 

A, E.

 

Second identification

 

B, C, D, E.

 

A.   Infrared absorption spectrophotometry (2.2.24).

 

Preparation. Dry the substances previously at 105 C for 6 h. Record the spectra using 4 mg of substance.

 

Comparison: Povidone CRS.

 

B.   To 0.4 ml of solution S1 (see Tests) add 10 ml of water  R, 5 ml of dilute hydrochloric acid R and 2 ml of potassium dichromate solution R. An orange-yellow precipitate is formed.

 

C.   To 1 ml of solution S1 add 0.2 ml of dimethylaminobenzaldehyde solution R1 and 0.1 ml of sulphuric acid R. A pink colour is produced.

 

D.   To 0.1 ml of solution S1 add 5 ml of water  R and 0.2 ml of 0.05 M iodine. A red colour is produced.

 

E.   It is freely soluble in water  R.

 

TESTS

 

Solution S

 

Dissolve 1.0 g in carbon dioxide-free water  R and dilute to 20 ml with the same solvent. Add the substance to be examined to the water in small portions with magnetic stirring.

 

Solution S1

 

Dissolve 2.5 g in carbon dioxide-free water  R and dilute to 25 ml with the same solvent. Add the substance to be examined to the water in small portions with magnetic stirring.

 

Appearance of solution

 

Solution S is clear  (2.2.1) and not more intensely coloured than reference solution B6, BY6 or R6 (2.2.2, Method II).

 

pH (2.2.3)

 

3.0 to 5.0 for solution S, for povidone having a stated K-value of at most 30; 4.0 to 7.0 for solution S, for povidone having a stated K-value of more than 30.

 

Aldehydes

 

Maximum 500 ppm, expressed as acetaldehyde.

 

Test solution

 

Dissolve 1.0 g of the substance to be examined in phosphate buffer solution pH 9.0 R and dilute to 100.0 ml with the same solvent. Stopper the flask and heat at 60 C for 1 h. Allow to cool.

 

Reference solution

 

Dissolve 0.140 g of acetaldehyde ammonia trimer trihydrate R in water  R and dilute to 200.0 ml with the same solvent. Dilute 1.0 ml of this solution to 100.0 ml with phosphate buffer solution pH 9.0 R.

 

Into 3 identical spectrophotometric cells with a path length of 1 cm, introduce separately 0.5 ml of the test solution, 0.5 ml of the reference solution and 0.5 ml of water  R (blank). To each cell, add 2.5 ml of phosphate buffer solution pH 9.0 R and 0.2 ml of nicotinamide-adenine dinucleotide solution R. Mix and stopper tightly. Allow to stand at 22 2 C for 2C3 min and measure the absorbance (2.2.25) of each solution at 340 nm, using water  R as the compensation liquid. To each cell, add 0.05 ml of aldehyde dehydrogenase solution R, mix and stopper tightly. Allow to stand at 22 2 C for 5 min. Measure the absorbance of each solution at 340 nm using water  R as the compensation liquid. Determine the content of aldehydes using the expression:

 

At1   =     absorbance of the test solution before the addition of aldehyde dehydrogenase,

 

At2   =     absorbance of the test solution after the addition of aldehyde dehydrogenase,

 

As1   =     absorbance of the reference solution before the addition of aldehyde dehydrogenase,

 

As2   =     absorbance of the reference solution after the addition of aldehyde dehydrogenase,

 

Ab1   =     absorbance of the blank before the addition of aldehyde dehydrogenase,

 

Ab2   =     absorbance of the blank after the addition of aldehyde dehydrogenase,

 

m    =     mass of povidone calculated with reference to the anhydrous substance, in grams,

 

C     =     concentration of acetaldehyde in the reference solution, calculated from the weight of the acetaldehyde ammonia trimer trihydrate with the factor 0.72, in milligrams per millilitre.

 

Peroxides

 

Maximum 400 ppm, expressed as H2O2.

 

Dissolve 2.0 g in 50 ml of water  R. To 25 ml of this solution, add 2 ml of titanium trichloride-sulphuric acid reagent R. Allow to stand for 30 min. The absorbance (2.2.25) of the solution, measured at 405 nm using a mixture of 25 ml of a 40 g/l solution of the substance to be examined and 2 ml of a 13 per cent V/V solution of sulphuric acid R as the compensation liquid, is not greater than 0.35.

 

Hydrazine

 

Thin-layer chromatography (2.2.27). Use freshly prepared solutions.

 

Test solution

 

Dissolve 2.5 g of the substance to be examined in 25 ml of water  R. Add 0.5 ml of a 50 g/l solution of salicylaldehyde R in methanol  R, mix and heat in a water-bath at 60 C for 15 min. Allow to cool, add 2.0 ml of toluene R, shake for 2 min and centrifuge. Use the clear  supernatant layer.

 

Reference solution

 

Dissolve 9 mg of salicylaldehyde azine R in toluene R and dilute to 100 ml with the same solvent. Dilute 1 ml of the solution to 10 ml with toluene R.

 

Plate

 

TLC silanised silica gel H plate R.

 

Mobile phase

 

Water R, methanol  R (1:2 V/V).

 

Application

 

10 ml.

 

Development

 

Over a path of 15 cm.

 

Drying

 

In air.

 

Detection

 

Examine in ultraviolet light at 365 nm.

 

Limit:

hydrazine: any spot corresponding to salicylaldehyde azine in the chromatogram obtained with the test solution is not more intense than the spot in the chromatogram obtained with the reference solution (1 ppm).

 

Impurity A

 

Liquid chromatography (2.2.29).

 

Test solution

 

Dissolve 0.25 g of the substance to be examined in the mobile phase and dilute to 10.0 ml with the mobile phase.

 

Reference solution (a)

 

Dissolve 50 mg of 1-vinylpyrrolidin-2-one R in methanol  R and dilute to 100.0 ml with the same solvent. Dilute 1.0 ml of the solution to 100.0 ml with methanol  R. Dilute 5.0 ml of this solution to 100.0 ml with the mobile phase.

 

Reference solution (b)

 

Dissolve 10 mg of 1-vinylpyrrolidin-2-one R and 0.5 g of vinyl acetate R in methanol  R and dilute to 100.0 ml with the same solvent. Dilute 1.0 ml of the solution to 100.0 ml with the mobile phase.

 

Precolumn:

size: l = 0.025 m, Ø = 4 mm,

 

stationary phase: octadecylsilyl silica gel for chromatography R (5 mm).

 

Column:

size: l = 0.25 m, Ø = 4 mm,

 

stationary phase: octadecylsilyl silica gel for chromatography R (5 mm),

 

temperature: 40 C.

 

Mobile phase

 

Acetonitrile R, water  R (10:90 V/V).

 

Flow rate

 

Adjusted so that the retention time of the peak corresponding to impurity A is about 10 min.

 

Detection

 

Spectrophotometer at 235 nm.

 

Injection

 

50 ml. After injection of the test solution, wait for about 2 min and wash the precolumn by passing the mobile phase backward, at the same flow rate applied in the test, for 30 min.

 

System suitability:

resolution: minimum 2.0 between the peaks due to impurity A and to vinyl acetate in the chromatogram obtained with reference solution (b),

 

repeatability: maximum relative standard deviation of 2.0 per cent after 5 injections of reference solution (a).

 

Limit:

impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (10 ppm).

 

Impurity B

 

 Liquid chromatography (2.2.29).

 

Test solution

 

Dissolve 100 mg of the substance to be examined in water  R and dilute to 50.0 ml with the same solvent.

 

Reference solution

 

Dissolve 100 mg of 2-pyrrolidone R in water  R and dilute to 100 ml with the same solvent. Dilute 3.0 ml to 50.0 ml with water  R.

 

Precolumn:

size: l = 0.025 m, Ø = 4 mm,

 

stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 mm).

 

Column:

size: l = 0.25 m, Ø = 4 mm,

 

stationary phase: spherical aminohexadecylsilyl silica gel for chromatography R (5 mm),

 

temperature: 30 C.

 

Mobile phase

 

Water R, adjusted to pH 2.4 with phosphoric acid R.

 

Flow rate

 

1 ml/min.

 

Detection

 

Spectrophotometer at 205 nm. A detector is placed between the precolumn and the analytical column. A second detector is placed after the analytical column.

 

Injection

 

10 ml. When impurity B has left the precolumn (after about 1.2 min) switch the flow directly from the pump to the analytical column. Before the next chromatogram is run, wash the precolumn by reversed flow.

 

Limit:

impurity B: not more than the area of the principal peak in the chromatogram obtained with the reference solution (3.0 per cent).

 

Heavy metals (2.4.8)

 

Maximum 10 ppm.

 

2.0 g complies with limit test D. Prepare the standard using 2.0 ml of lead standard solution (10 ppm Pb) R.

 

Water (2.5.12)

 

Maximum 5.0 per cent, determined on 0.500 g.

 

Sulphated ash (2.4.14)

 

Maximum 0.1 per cent, determined on 1.0 g.

 

Viscosity, expressed as K-value

 

For povidone having a stated value of 18 or less, use a 50 g/l solution. For povidone having a declared value of more than 18, use a 10 g/l solution. For povidone having a declared value of more than 95, use a 1.0 g/l solution. Allow to stand for 1 h and determine the viscosity (2.2.9) of the solution at 25 C, using viscometer No.1 with a minimum flow time of 100 s. Calculate the K-value from the expression:

 

c     =     concentration of the substance to be examined, calculated with reference to the anhydrous substance, in g/100 ml, 

h     =     viscosity of the solution relative to that of water R.     

ASSAY

 

Place 100.0 mg of the substance to be examined (m mg) in a combustion flask, add 5 g of a mixture of 1 g of copper sulphate R, 1 g of titanium dioxide R and 33 g of dipotassium sulphate R, and 3 glass beads. Wash any adhering particles from the neck into the flask with a small quantity of water  R. Add 7 ml of sulphuric acid R, allowing it to run down the sides of the flask, and mix the contents by rotation. Close the mouth of the flask loosely, for example by means of a glass bulb with a short stem, to avoid excessive loss of sulphuric acid. Heat gradually at first, then increase the temperature until there is vigorous boiling with condensation of sulphuric acid in the neck of the flask; precautions are to be taken to prevent the upper part of the flask from becoming overheated. Continue the heating for 45 min. Cool, dissolve the solid material by cautiously adding to the mixture 20 ml of water  R, cool again and place in a steam-distillation apparatus. Add 30 ml of strong sodium hydroxide solution R through the funnel, rinse cautiously the funnel with 10 ml of water  R and distil immediately by passing steam through the mixture. Collect about 80-100 ml of distillate in a mixture of 30 ml of a 40 g/l solution of boric acid R and 3 drops of bromocresol green-methyl red solution R and enough water  R to cover the tip of the condenser. Towards the end of the distillation lower the receiver so that the tip of the condenser is above the surface of the acid solution and rinse the end part of the condenser with a small quantity of water  R. Titrate the distillate with 0.025 M sulphuric acid until the colour of the solution changes from green through pale greyish-blue to pale greyish-red-purple (n1 ml of 0.025 M sulphuric acid).

 

Repeat the test using about 100.0 mg of glucose R in place of the substance to be examined (n2 ml of 0.025 M sulphuric acid).

 

STORAGE

 

In an airtight container .

 

LABELLING

 

The label indicates the nominal K-value.

 

IMPURITIES

 

A.   R = CH=CH2: 1-ethenylpyrrolidin-2-one (1-vinylpyrrolidin-2-one),

 

B.   R = H: pyrrolidin-2-one (2-pyrrolidone).

 

 


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Action and use

 

Pharmaceutical aid.