»Povidone is a synthetic polymer consisting essentially of linear 1-vinyl-2-pyrrolidinone groups,the degree of polymerization of which results in polymers of various molecular weights.The different types of Povidone are characterized by their viscosity in aqueous solution,relative to that of water,expressed as a K-value.(See the section on K-value below.)The K-value of Povidone having a stated (nominal)K-value of 15or less is not less than 85.0percent and not more than 115.0percent of the stated values.The K-value of Povidone having a stated K-value or a stated K-value range with an average of more than 15is not less than 90.0percent and not more than 108.0percent of the stated value or of the average of the stated range.
Packaging and storage Preserve in tight containers.
Labeling Label it to state,as part of the official title,the K-value or K-value range of the Povidone.
A: To 10mLof a solution (1in 50)add 20mLof 1Nhydrochloric acid and 5mLof potassium dichromate TS:an orange-yellow precipitate is formed.
B: Dissolve 75mg of cobalt nitrate and 300mg of ammonium thiocyanate in 2mLof water.To this solution add 5mLof a solution of Povidone (1in 50),and render the resulting solution acid by the addition of 3Nhydrochloric acid:a pale blue precipitate is formed.
C: To 5mLof a solution (1in 200)add a few drops of iodine TS:a deep red color is produced.
pHá791ñ: between 3.0and 7.0,in a solution (1in 20).
Water,Method Iá921ñ: not more than 5.0%.
Residue on ignition á281ñ: not more than 0.1%.
Lead á251ñ Dissolve 1.0g in 25mLof water:the limit is 10ppm.
Limit of aldehydes
Phosphate buffer Transfer 8.3g of potassium pyrophosphate to a 500-mLvolumetric flask,and dissolve in 400mLof water.Adjust,if necessary,with 1Nhydrochloric acid to a pHof 9.0,dilute with water to volume,and mix.
Aldehyde dehydrogenase solution Transfer a quantity of lyophilized aldehyde dehydrogenase equivalent to 70units to a glass vial,dissolve in 10.0mLof water,and mix.[NOTEThis solution is stable for 8hours at 4.]
NADsolution Transfer 40mg of nicotinamide adenine dinucleotide to a glass vial,dissolve in 10.0mLof Phosphate buffer,and mix.[NOTEThis solution is stable for 4weeks at 4.]
Standard preparation Add about 2mLof water to a glass weighing bottle,and weigh accurately.Add about 100mg (about 0.13mL)of freshly distilled acetaldehyde,and weigh accurately.Transfer this solution to a 100-mLvolumetric flask.Rinse the weighing bottle with several portions of water,transferring each rinsing to the 100-mLvolumetric flask.Dilute the solution in the 100-mLvolumetric flask with water to volume,and mix.Store at 4for about 20hours.Pipet 1mLof this solution into a 100-mLvolumetric flask,dilute with water to volume,and mix.
Test preparation Transfer about 2g of Povidone,accurately weighed,to a 100-mLvolumetric flask,dissolve in 50mLof Phosphate buffer,dilute with Phosphate bufferto volume,and mix.Insert a stopper into the flask,heat at 60for 1hour,and cool to room temperature.
Procedure Pipet 0.5mLeach of the Standard preparation,the Test preparation,and water to provide the reagent blank into separate 1-cm cells.Add 2.5mLof Phosphate bufferand 0.2mLof NADsolutionto each cell.Cover the cells to exclude oxygen.Mix by inversion,and allow to stand for 2to 3minutes at 22±2.Determine the absorbances of the solutions at a wavelength of 340nm,using water as the reference.Add 0.05mLof Aldehyde dehydrogenase solutionto each cell.Cover the cells to exclude oxygen.Mix by inversion,and allow to stand for 5minutes at 22±2.Determine the absorbances of the solutions at a wavelength of 340nm,using water as the reference.Calculate the percentage of aldehydes,expressed as acetaldehyde,in the Povidone taken by the formula: Cis the concentration,in mg per mL,of acetaldehyde in the Standard preparation;Wis the weight,in g,of Povidone taken;AU1,AS1,and AB1are the absorbances of the solutions obtained from the Test preparation,Standard preparation,and water reagent blank,respectively,before addition of the Aldehyde dehydrogenase solution;and AU2,AS2,and AB2are the absorbances of the solutions obtained from the Test preparation,Standard preparation,and water reagent blank,respectively,after addition of the Aldehyde dehydrogenase solution:not more than 0.05%is found.
Limit of hydrazine Transfer 2.5g to a 50-mLcentrifuge tube,add 25mLof water,and mix to dissolve.Add 500µLof a 1in 20solution of salicylaldehyde in methanol,swirl,and heat in a water bath at 60for 15minutes.Allow to cool,add 2.0mLof toluene,insert a stopper in the tube,shake vigorously for 2minutes,and centrifuge.Apply 10µLof the clear upper toluene layer in the centrifuge tube and 10µLof a Standard solution of salicylaldazine in toluene containing 9.38µg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of dimethylsilanized chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of methanol and water (2:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by examination under UVlight at a wavelength of 365nm:salicylaldazine appears as a fluorescent spot having an RFvalue of about 0.3,and the fluorescence of any salicylaldazine spot from the test specimen is not more intense than that produced by the spot obtained from the Standard solution (1ppm of hydrazine).
Mobile phase Prepare a mixture of methanol and water (20:80).
System suitability solution Transfer 10mg of vinylpyrrolidinone and 500mg of vinyl acetate,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume.Transfer 1.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Standard preparation Transfer an accurately weighed quantity of 50mg of vinylpyrrolidinone to a 100-mLvolumetric flask,dilute with methanol to volume,and mix.Transfer 1.0-mLof this solution to a 100-mLvolumetric flask,dilute with methanol to volume,and mix.Transfer 5.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phase to volume,and mix.
Test preparation Transfer an accurately weighed quantity of about 250mg of Povidone to a 10-mLvolumetric flask,dilute withMobile phase to volume,and mix.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a 235-nm detector,a 4.0-mm ×2.5-cm guard column containing packing L7,and a 4.0-mm ×25-cm analytical column containing 5-µm packing L7.The column temperature is maintained at about 40.Adjust the flow rate so that the retention time of vinylpyrrolidinone is about 10minutes.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the resolution,R,between vinylpyrrolidinone and vinyl acetate is not less than 2.0.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 50µL)each of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the vinylpyrrolidinone peak.[NOTEIf necessary,after each injection of the Test preparation,wash the polymeric material of Povidone from the guard column by passing the Mobile phase through the column backwards for about 30minutes at the same flow rate.]Calculate the percentage of vinylpyrrolidinone in the sample taken by the formula:
1000(C/W)(rU/rS),in which Cis the concentration,in mg per mL,of vinylpyrrolidinone in the Standard preparation;Wis the weight,in mg,of Povidone taken to prepare the Test preparation;and rUand rSare the peak responses for vinylpyrrolidinone obtained from the Test preparationand Standard preparation,respectively:not more than 0.001%is found.
K-value Weigh accurately a quantity of undried Povidone equivalent on the anhydrous basis to the amount specified in the following table:
Dissolve it in about 50mLof water in a 100-mLvolumetric flask,dilute with water to volume,and mix.Allow to stand for 1hour.Determine the viscosity,using a capillary-tube viscosimeter (see Viscosity á911ñ)of this solution at 25±0.2.Calculate the K-value of Povidone by the formula:
in which cis the weight,in g,on the anhydrous basis,of the specimen tested in each 100.0mLof solution;and zis the viscosity of the test solution relative to that of water.
Nitrogen content Proceed as directed under Nitrogen Determination,Method IIá461ñ,using about 0.1g of Povidone,accurately weighed.In the procedure,omit the use of hydrogen peroxide,use 5g of a powdered mixture of potassium sulfate,cupric sulfate,and titanium dioxide (33:1:1),instead of potassium sulfate and cupric sulfate (10:1),and heat until a clear,light-green solution is obtained,then heat for a further 45minutes:the nitrogen content,on the anhydrous basis,is not less than 11.5%and not more than 12.8%.
Auxiliary Information Staff Liaison:Justin Lane,B.S.,Scientific Associate
Expert Committee:(EMC)Excipients:Monograph Content
USP28NF23Page 1600Pharmacopeial Forum:Volume No.30(4)Page 1292