交联聚维酮-USP35

NF 30Official Monographs / Crospovidone1775F= factor converting glycolic acid to sodium and yeasts count does not exceed 100 cfu/g. It meets the glycolate, 12.9requirements of the tests for absence of Escherichia coli.W1= weight of glycolic acid in the specimen (mg),•P H 〈791〉: The pH of the dispersion is 5.0–7.0. Mix 1g with determined from the standard curve and the100 mL of water for 5 min.absorbance of the Sample solution•S ETTLING V OLUMEb= percentage of Loss on Drying, determined Analysis: To 75 mL of water in a 100-mL graduated separately cylinder, add 1.5 g of it in 0.5-g portions, shaking W2= weight of the specimen taken (g)vigorously after each addition. Add water to make 100 mL, Acceptance criteria: The sum of the percentages of shake again until all of the powder is homogeneouslysodium chloride and sodium glycolate is NMT 0.5%.distributed, and allow to stand for 4 h. Note the volume ofthe settled mass.SPECIFIC TESTS Acceptance criteria: The volume of the settled mass is•C ONTENT OF W ATER-S OLUBLE M ATERIAL10.0–30.0 mLAnalysis: Disperse 10g in 800 mL of water, and stir for 1min every 10 min during the first 30 min. Allow to stand for ADDITIONAL REQUIREMENTSan additional h, or centrifuge, if necessary. Decant 200 mL•P ACKAGING AND S TORAGE: Preserve in well-closed containers.of the aqueous slurry onto a rapid-filtering filter paper in a No storage requirements specified.vacuum 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; again Crospovidoneweigh; and calculate the weight, in g, of residue W1, by Portions of the monograph text that are national USP text, and difference.are not part of the harmonized text, are marked with symbolsCalculate the percentage of water-soluble material in the(33) to specify this fact.specimen, 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)(C6H9NO)nb= percentage Loss on Drying of the specimen taken1-Ethenyl-2-pyrrolidinone homopolymer;Acceptance criteria: NMT 10.0%1-Vinyl-2-pyrrolidinone homopolymer [9003-39-8].•D EGREE OF S UBSTITUTIONDEFINITIONSample: 1gCrospovidone is a water-insoluble synthetic cross-linked homo-Analysis: Transfer the Sample to a glass-stoppered, 500-mLpolymer of N-vinyl-2-pyrrolidinone. It contains NLT 11.0% conical flask. Add 300 mL of sodium chloride solution (1 inand NMT 12.8% of nitrogen (N), calculated on the dried10), then add 25.0 mL of 0.1 N sodium hydroxide VS. Insertbasis. Two types of Crospovidone are available, depending on the stopper, and allow to stand for 5 min with intermittentthe particle size: Type A and Type B.shaking. Add 5 drops of m-cresol purple TS, and from aburet add 15 mL of 0.1 N hydrochloric acid VS. Insert theIDENTIFICATIONstopper in the flask, and shake. If the solution is violet, add•3A. I NFRARED A BSORPTION〈197K〉: Previously dried in a vac-0.1 N hydrochloric acid VS in 1-mL portions until theuum at 105° for 1 h3solution becomes yellow, shaking after each addition. Titrate•B.with 0.1 N sodium hydroxide VS to a violet endpoint.Sample: 1gCalculate the net number of milliequivalents, M, of baseAnalysis: Suspend the Sample in 10 mL of water, add 0.1 required for the neutralization of 1g of CroscarmellosemL of 0.1 N iodine, and shake for 30 s. Add 1 mL of starch Sodium, on the dried basis.TS, and shake.Calculate the degree of acid carboxymethyl substitution, A:Acceptance criteria: No blue color develops.•C. To 10 mL of water add 0.1 g and shake. A suspension is Result = 1150 × M/[7102 − (412 × M) − (80 × C)]formed, and no clear solution is obtained within 15 min.•D.M= milliequivalentsSample: 20g of the dried substance C= percentage of Residue on Ignition of theAnalysis: Clean and dry the analytical sieves used in the Croscarmellose Sodium as determined in theanalysis by washing the sieves in hot water. Allow to dry test for Residue on Ignitionovernight in a drying cabinet at 105°. Place the Sample in a Calculate the degree of sodium carboxymethyl substitution,1000-mL conical flask, add 500 mL of water, and shake the S:suspension for 30 min. Pour the suspension through a 63-Result = [162 + (58 × A)] × C/[7102 − (80 × C)]µm analytical sieve, previously tared, and rinse the sievewith water until the filtrate is clear. Dry the sieve and sam-A= degree of acid carboxymethyl substitution, as ple residue at 105° for 5 h in a drying cabinet without circu-determined above lating air. Cool in a desiccator for 30 min, and weigh.C= percentage of Residue on Ignition of the Calculate the percentage sieving residue fraction of sample Croscarmellose Sodium as determined in the particles having a diameter of more than 63 µm:test for Residue on IgnitionThe degree of substitution is the sum of A + S.Result = [(m1−m3) × 100]/m2 Acceptance criteria: The degree of substitution ism1= mass of the sieve and sample residue, after0.60–0.85, on the dried basisdrying for 5 h (g)•L OSS ON D RYING〈731〉: Dry a sample at 105° for 6 h: it losesm3= mass of the sieve (g)NMT 10.0% of its weight.m2= initial mass of the sample, calculated on a dried •M ICROBIAL E NUMERATION T ESTS〈61〉and T ESTS FOR S PECIFIEDbasis (g)M ICROORGANISMS〈62〉: The total aerobic microbial countdoes not exceed 1000 cfu/g, and the total combined molds1776Crospovidone / Official Monographs NF 30Acceptance criteria: If the sieving residue fraction is more Relative standard deviation: NMT 2.0% for 6 injections, than 15%, the substance is classified as Type A; if the sieving Reference solution Aresidue fraction is NMT 15%, the substance is classified as AnalysisType B.Samples:Sample solution and Reference solution ARecord the chromatograms, and measure the responses for ASSAY the vinylpyrrolidinone peak.•N ITROGEN D ETERMINATION, Method II〈461〉Acceptance criteria: The area of the peak from the Sample Sample: 0.1 g solution is NMT the area of the principal peak from Reference Analysis: Proceed as directed, using the Sample. In the solution A (NMT 10 ppm).Procedure, omit the use of hydrogen peroxide, and use 5gof a powdered mixture of potassium sulfate, cupric sulfate,SPECIFIC TESTSand titanium dioxide (33:1:1), instead of potassium sulfate•L OSS ON D RYING〈731〉: Dry 0.5 g at 105° to constant and cupric sulfate (10:1). Heat until a clear, light green weight: it loses NMT 5.0% of its weight.solution is obtained. Heat for an additional 45 min, and•W ATER-S OLUBLE S UBSTANCESproceed as directed for Procedure, beginning with Sample: 25.0 g“Cautiously add to the digestion mixture 70 mL of water”.Analysis: Transfer the Sample to a 400-mL beaker, add 200 Acceptance criteria: 11.0%–12.8% on the dried basis mL of water, and stir on a magnetic stirrer, using a 5-cmstirring bar, for 1 h. Transfer to a 250-mL volumetric flask IMPURITIES with the aid of 25 mL of water. Add water to volume. Allow •R ESIDUE ON I GNITION〈281〉: NMT 0.1%, determined on 1.0 g the bulk of the solids to settle. Pass 100 mL of the relatively •3H EAVY M ETALS, Method II〈231〉: NMT 10 ppm3clear supernatant through a membrane filter of 0.45-µm •P EROXIDES pore size, protected against clogging by superimposing a Sample suspension A: [N OTE—Use for Type A.]membrane filter of 3-µm pore size. While filtering, stir the40 mg/mL in water. To 25 mL of this suspension add 2 mL solution above the filter manually or with a mechanicalof titanium trichloride–sulfuric acid TS. Allow to stand for stirrer, taking care not to physically damage the membrane30 min, and filter.filter. Transfer 50.0 mL of the clear filtrate to a tared 100-mL Sample suspension B: [N OTE—Use for Type B.]beaker, evaporate to dryness, and dry at 110° for 3 h.16 mg/mL in water. To 25 mL of this suspension add 2 mL Acceptance criteria: The weight of the residue does notof titanium trichloride–sulfuric acid TS. Allow to stand for exceed 75 mg (1.5%).30 min, and filter.Compensation liquid A: [N OTE—Use for Type A.]ADDITIONAL REQUIREMENTS40 mg/mL in water. Filter, take 25 mL, and add 2 mL of a•3P ACKAGING AND S TORAGE: Preserve in tight containers.313% solution of sulfuric acid.•3L ABELING: The label states the type (Type A or Type B).3 Compensation liquid B: [N OTE—Use for Type B.]•3USP R EFERENCE S TANDARDS〈11〉16 mg/mL in water. Filter, take 25 mL, and add 2 mL of a USP Crospovidone RS313% 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 Type Gamma CyclodextrinB, this corresponds to NMT 1000 ppm expressed as H2O2.•V INYLPYRROLIDINONEMobile 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: LC(C6H10O5)81297.12 Detector: UV Cyclooctaamylose;Analytical wavelength: 235 nm Cyclomaltooctaose [17465-86-0].Precolumn: 4-mm × 2.5-cm; 5-µm packing L1Column: 4-mm × 25-cm; 5-µm packing L1DEFINITIONColumn temperature: 40°Gamma Cyclodextrin is composed of 8 alpha-(1–4) linked D-Flow rate: 1 mL/min glycopyranosyl units. It contains NLT 98.0% and NMT Injection size: 50 µL. [N OTE—After each injection of the102.0% of cyclooctaamylose (C6H10O5)8, calculated on the Sample solution, wash the precolumn by passing the Mobile dried basis.phase backwards, at the same flow rate as applied in theIDENTIFICATIONtest, for 30 min.]•A. I NFRARED A BSORPTION〈197K〉System suitability•B. The retention time of the major peak from the Sample Samples:Reference solution A and Reference solution Bsolution corresponds to that of the Standard solution, as ob-Suitability requirementstained in the Assay.Resolution: NLT 2.0 between vinylpyrrolidone and vinylacetate, Reference solution B。