Indomethacin Capsules
» Indomethacin Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C19H16ClNO4.
Packaging and storage— Preserve in well-closed containers.
USP Reference standards 11
USP Indomethacin RS Click to View Structure
Identification—
A: Shake a portion of the contents of Capsules, equivalent to about 50 mg of indomethacin, with 10 mL of acetone for about 2 minutes, and filter. Transfer 5 mL of the filtrate to a stoppered flask, add 20 mL of water, and shake for about 2 minutes until a precipitate forms and crystallizes. Filter, and collect the crystals. Dry the crystals in air, then dry at a pressure below 5 mm of mercury at 100 for 2 hours: the IR absorption spectrum of a potassium bromide dispersion of the dried residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Indomethacin RS that has been similarly recrystallized from a solution of 25 mg in 5 mL of acetone.
B: Shake a portion of the contents of Capsules, equivalent to about 25 mg of indomethacin, with 25 mL of methanol, and filter. Separately apply 2 µL of the filtrate so obtained (test solution) and 2 µL of a Standard solution in methanol containing 1 mg of USP Indomethacin RS per mL to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture, and dry the spots with the aid of a current of air. Develop the chromatogram in a solvent system consisting of a mixture of chloroform and methanol (4:1) 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, allow it to dry, and locate the spots under short-wavelength UV light: the intensity and RF value of the principal spot obtained from the test solution correspond to that obtained from the Standard solution.
Dissolution 711
Medium: 1 volume of pH 7.2 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions) mixed with 4 volumes of water; 750 mL.
Apparatus 1: 100 rpm.
Time: 20 minutes.
Procedure— Determine the amount of C19H16ClNO4 dissolved from UV absorbances at the wavelength of maximum absorbance at about 318 nm of filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Indomethacin RS in the same medium.
Tolerances— Not less than 80% (Q) of the labeled amount of C19H16ClNO4 is dissolved in 20 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity— Transfer the contents of 1 Capsule to a 100-mL volumetric flask, add 10 mL of water, and allow to stand for 10 minutes, swirling occasionally. Add 60 mL of methanol, shake for 10 minutes, dilute with methanol to volume, mix, and centrifuge. Dilute a portion of the clear solution quantitatively and stepwise, if necessary, with a mixture of equal volumes of methanol and pH 7.0 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions) to obtain a solution containing about 25 µg of indomethacin per mL. Concomitantly determine the absorbances of this solution and a Standard solution of USP Indomethacin RS, in the methanol and pH 7.0 phosphate buffer mixture (1:1) having a known concentration of about 25 µg per mL, in 1-cm cells at the wavelength of maximum absorbance at about 318 nm, with a suitable spectrophotometer, using the methanol and pH 7.0 phosphate buffer mixture as the blank. Calculate the quantity, in mg, of C19H16ClNO4 in the Capsule taken by the formula:
(TC / D)(AU / AS)
in which T is the labeled quantity, in mg, of indomethacin in the Capsule, C is the concentration, in µg per mL, of USP Indomethacin RS in the Standard solution, D is the concentration, in µg per mL, of indomethacin in the test solution, based upon the labeled quantity per Capsule and the extent of dilution, and AU and AS are the absorbances of the solution from the Capsule and the Standard solution, respectively.
Assay
Standard preparation— Transfer about 25 mg of USP Indomethacin RS, accurately weighed, to a 200-mL volumetric flask, dissolve in 2 mL of methanol, dilute with pH 7.2 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions) to volume, and mix. Transfer 25.0 mL of this solution to a separator, and extract with three 25-mL portions of methylene chloride. Filter the extracts through a pledget of cotton into a 100-mL volumetric flask, rinse the filter with methylene chloride, dilute with methylene chloride to volume, and mix to obtain a Standard preparation having a known concentration of about 31 µg per mL.
Assay preparation— Transfer, as completely as possible, the contents of not less than 20 Capsules to a suitable tared container, and determine the average content weight per Capsule. Mix the combined contents, and transfer an accurately weighed portion, equivalent to about 25 mg of indomethacin, to a 200-mL volumetric flask, add 2 mL of methanol, shake for 10 minutes, dilute with pH 7.2 phosphate buffer to volume, and mix. Transfer about 50 mL to a centrifuge tube, and centrifuge for 15 minutes. Transfer 25.0 mL of the supernatant to a 125-mL separator, and extract with three 25-mL portions of methylene chloride. Filter the extracts through a pledget of cotton into a 100-mL volumetric flask, rinse the filter with methylene chloride, dilute with methylene chloride to volume, and mix.
Procedure— Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 318 nm, with a suitable spectrophotometer, using methylene chloride as the blank. Calculate the quantity, in mg, of C19H16ClNO4 in the portion of Capsules taken by the formula:
0.8C(AU / AS)
in which C is the concentration, in µg per mL, of USP Indomethacin RS in the Standard preparation; and AU and AS are the absorbances of the Assay preparation and the Standard preparation, respectively.
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Topic/Question Contact Expert Committee
Monograph Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison
1-301-816-8139
(SM22010) Monographs - Small Molecules 2
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711 Margareth R.C. Marques, Ph.D.
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(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 3497