Accessed from 128.83.63.20 by nEwp0rt1 on Tue Nov 29 21:22:37 EST 2011NF 30= factor converting glycolic acid to sodiumglycolate, 12.9W1= weight of glycolic acid in the specimen (mg),determined from the standard curve and theabsorbance of the Sample solutionb= percentage of Loss on Drying, determinedseparatelyW2= weight of the specimen taken (g)Acceptance criteria: The sum of the percentages ofsodium chloride and sodium glycolate is NMT 0.5%.SPECIFIC TESTS•CONTENT OF WATER-SOLUBLE MATERIALAnalysis: Disperse 10g in 800 mL of water, and stir for 1min every 10 min during the first 30 min. Allow to stand foran additional h, or centrifuge, if necessary. Decant 200 mLof the aqueous slurry onto a rapid-filtering filter paper in avacuum filtration funnel, apply vacuum, and collect about150 mL of the filtrate. Pour the filtrate into a tared 250-mLbeaker, weigh, and calculate the weight, in g, of the filtrate,W3, by difference. Concentrate on a hot plate to a smallvolume, but not to dryness; dry at 105° for 4 h; againweigh; and calculate the weight, in g, of residue W1, bydifference.Calculate the percentage of water-soluble material in thespecimen, on the dried basis, taken:Result = [100 × W1 × (800 + W2)]/{W2 × W3 × [1 − (0.01 ×b)]}W1= weight of residue by difference (g)W2= weight of the specimen taken (g)W3= weight of the filtrate by difference (g)b= percentage Loss on Drying of the specimen takenAcceptance criteria: NMT 10.0%•DEGREE OF SUBSTITUTIONSample: 1gAnalysis: Transfer the Sample to a glass-stoppered, 500-mLconical flask. Add 300 mL of sodium chloride solution (1 in10), then add 25.0 mL of 0.1 N sodium hydroxide VS. Insertthe stopper, and allow to stand for 5 min with intermittentshaking. Add 5 drops of m-cresol purple TS, and from aburet add 15 mL of 0.1 N hydrochloric acid VS. Insert thestopper in the flask, and shake. If the solution is violet, add0.1 N hydrochloric acid VS in 1-mL portions until thesolution becomes yellow, shaking after each addition. Titratewith 0.1 N sodium hydroxide VS to a violet endpoint.Calculate the net number of milliequivalents, M, of baserequired for the neutralization of 1g of CroscarmelloseSodium, on the dried basis.Calculate the degree of acid carboxymethyl substitution, A:Result = 1150 × M/[7102 − (412 × M) − (80 × C)]MC= milliequivalents= percentage of Residue on Ignition of theCroscarmellose Sodium as determined in thetest for Residue on IgnitionCalculate the degree of sodium carboxymethyl substitution,S:Result = [162 + (58 × A)] × C/[7102 − (80 × C)]= degree of acid carboxymethyl substitution, asdetermined aboveC= percentage of Residue on Ignition of theCroscarmellose Sodium as determined in thetest for Residue on IgnitionThe degree of substitution is the sum of A + S.Acceptance criteria: The degree of substitution is0.60–0.85, on the dried basis•LOSS ON DRYING 〈731〉: Dry a sample at 105° for 6 h: it losesNMT 10.0% of its weight.•MICROBIAL ENUMERATION TESTS 〈61〉 and TESTS FOR SPECIFIEDMICROORGANISMS 〈62〉: The total aerobic microbial countdoes not exceed 1000 cfu/g, and the total combined moldsAFOfficial Monographs / Crospovidone1775and yeasts count does not exceed 100 cfu/g. It meets therequirements of the tests for absence of Escherichia coli.•PH 〈791〉: The pH of the dispersion is 5.0–7.0. Mix 1g with100 mL of water for 5 min.•SETTLING VOLUMEAnalysis: To 75 mL of water in a 100-mL graduatedcylinder, add 1.5 g of it in 0.5-g portions, shakingvigorously after each addition. Add water to make 100 mL,shake again until all of the powder is homogeneouslydistributed, and allow to stand for 4 h. Note the volume ofthe settled mass.Acceptance criteria: The volume of the settled mass is10.0–30.0 mLADDITIONAL REQUIREMENTS•PACKAGING AND STORAGE: Preserve in well-closed containers.No storage requirements specified.CrospovidonePortions of the monograph text that are national USP text, andare not part of the harmonized text, are marked with symbols(33) to specify this fact.(C6H9NO)n1-Ethenyl-2-pyrrolidinone homopolymer;1-Vinyl-2-pyrrolidinone homopolymer [9003-39-8].DEFINITIONCrospovidone is a water-insoluble synthetic cross-linked homo-polymer of N-vinyl-2-pyrrolidinone. It contains NLT 11.0%and NMT 12.8% of nitrogen (N), calculated on the driedbasis. Two types of Crospovidone are available, depending onthe particle size: Type A and Type B.IDENTIFICATION•3A. INFRARED ABSORPTION 〈197K〉: Previously dried in a vac-uum at 105° for 1 h3•B.Sample: 1gAnalysis: Suspend the Sample in 10 mL of water, add 0.1mL of 0.1 N iodine, and shake for 30 s. Add 1 mL of starchTS, and shake.Acceptance criteria: No blue color develops.•C. To 10 mL of water add 0.1 g and shake. A suspension isformed, and no clear solution is obtained within 15 min.•D.Sample: 20g of the dried substanceAnalysis: Clean and dry the analytical sieves used in theanalysis by washing the sieves in hot water. Allow to dryovernight in a drying cabinet at 105°. Place the Sample in a1000-mL conical flask, add 500 mL of water, and shake thesuspension for 30 min. Pour the suspension through a 63-µm analytical sieve, previously tared, and rinse the sievewith water until the filtrate is clear. Dry the sieve and sam-ple residue at 105° for 5 h in a drying cabinet without circu-lating air. Cool in a desiccator for 30 min, and weigh.Calculate the percentage sieving residue fraction of sampleparticles having a diameter of more than 63 µm:Result = [(m1 − m3) × 100]/m2m1m3m2= mass of the sieve and sample residue, afterdrying for 5 h (g)= mass of the sieve (g)= initial mass of the sample, calculated on a driedbasis (g)Official from May 1, 2012Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.Accessed from 128.83.63.20 by nEwp0rt1 on Tue Nov 29 21:22:37 EST 20111776Crospovidone / Official MonographsAcceptance criteria: If the sieving residue fraction is morethan 15%, the substance is classified as Type A; if the sievingresidue fraction is NMT 15%, the substance is classified asType B.ASSAY•NITROGEN DETERMINATION, Method II 〈461〉Sample: 0.1 gAnalysis: Proceed as directed, using the Sample. In theProcedure, omit the use of hydrogen peroxide, and use 5gof a powdered mixture of potassium sulfate, cupric sulfate,and titanium dioxide (33:1:1), instead of potassium sulfateand cupric sulfate (10:1). Heat until a clear, light greensolution is obtained. Heat for an additional 45 min, andproceed as directed for Procedure, beginning with“Cautiously add to the digestion mixture 70 mL of water”.Acceptance criteria: 11.0%–12.8% on the dried basisIMPURITIES•RESIDUE ON IGNITION 〈281〉: NMT 0.1%, determined on 1.0 g•3HEAVY METALS, Method II 〈231〉: NMT 10 ppm3•PEROXIDESSample suspension A: [NOTE—Use for Type A.]40 mg/mL in water. To 25 mL of this suspension add 2 mLof titanium trichloride–sulfuric acid TS. Allow to stand for30 min, and filter.Sample suspension B: [NOTE—Use for Type B.]16 mg/mL in water. To 25 mL of this suspension add 2 mLof titanium trichloride–sulfuric acid TS. Allow to stand for30 min, and filter.Compensation liquid A: [NOTE—Use for Type A.]40 mg/mL in water. Filter, take 25 mL, and add 2 mL of a13% solution of sulfuric acid.Compensation liquid B: [NOTE—Use for Type B.]16 mg/mL in water. Filter, take 25 mL, and add 2 mL of a13% solution of sulfuric acid.Analysis: Measure the absorbance of the filtrate at 405 nmagainst the appropriate compensation liquid.Acceptance criteria: NMT 0.35. For Type A, thiscorresponds to NMT 400 ppm expressed as H2O2; for TypeB, this corresponds to NMT 1000 ppm expressed as H2O2.•VINYLPYRROLIDINONEMobile phase: Acetonitrile and water (1:9)Sample solution: 25 mg/mL of suspension in methanol.Shake for 60 min. Leave the bulk to settle, and pass througha filter of 0.2-µm pore size.Reference stock solution A: 5 µg/mL of vinylpyrrolidinonein methanolReference stock solution B: 100 µg/mL ofvinylpyrrolidinone and 5 mg/mL of vinyl acetate in methanolReference solution A: A 1-in-20 solution of Reference stocksolution A in Mobile phaseReference solution B: A 1-in-100 solution of Reference stocksolution B in Mobile phaseChromatographic system(See Chromatography 〈621〉, System Suitability.)Mode: LCDetector: UVAnalytical wavelength: 235 nmPrecolumn: 4-mm × 2.5-cm; 5-µm packing L1Column: 4-mm × 25-cm; 5-µm packing L1Column temperature: 40°Flow rate: 1 mL/minInjection size: 50 µL. [NOTE—After each injection of theSample solution, wash the precolumn by passing the Mobilephase backwards, at the same flow rate as applied in thetest, for 30 min.]System suitabilitySamples: Reference solution A and Reference solution BSuitability requirementsResolution: NLT 2.0 between vinylpyrrolidone and vinylacetate, Reference solution BNF 30Relative standard deviation: NMT 2.0% for 6 injections,Reference solution AAnalysisSamples: Sample solution and Reference solution ARecord the chromatograms, and measure the responses forthe vinylpyrrolidinone peak.Acceptance criteria: The area of the peak from the Samplesolution is NMT the area of the principal peak from Referencesolution A (NMT 10 ppm).SPECIFIC TESTS•LOSS ON DRYING 〈731〉: Dry 0.5 g at 105° to constantweight: it loses NMT 5.0% of its weight.•WATER-SOLUBLE SUBSTANCESSample: 25.0 gAnalysis: Transfer the Sample to a 400-mL beaker, add 200mL of water, and stir on a magnetic stirrer, using a 5-cmstirring bar, for 1 h. Transfer to a 250-mL volumetric flaskwith the aid of 25 mL of water. Add water to volume. Allowthe bulk of the solids to settle. Pass 100 mL of the relativelyclear supernatant through a membrane filter of 0.45-µmpore size, protected against clogging by superimposing amembrane filter of 3-µm pore size. While filtering, stir thesolution above the filter manually or with a mechanicalstirrer, taking care not to physically damage the membranefilter. Transfer 50.0 mL of the clear filtrate to a tared 100-mLbeaker, evaporate to dryness, and dry at 110° for 3 h.Acceptance criteria: The weight of the residue does notexceed 75 mg (1.5%).ADDITIONAL REQUIREMENTS•3PACKAGING AND STORAGE: Preserve in tight containers.3•3LABELING: The label states the type (Type A or Type B).3•3USP REFERENCE STANDARDS 〈11〉USP Crospovidone RS3Gamma Cyclodextrin (C6H10O5)8Cyclooctaamylose;Cyclomaltooctaose [17465-86-0].1297.12DEFINITIONGamma Cyclodextrin is composed of 8 alpha-(1–4) linked D-glycopyranosyl units. It contains NLT 98.0% and NMT102.0% of cyclooctaamylose (C6H10O5)8, calculated on thedried basis.IDENTIFICATION•A. INFRARED ABSORPTION 〈197K〉•B. The retention time of the major peak from the Samplesolution corresponds to that of the Standard solution, as ob-tained in the Assay.Official from May 1, 2012Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved.