A: The contents of Capsules respond to the Identificationtests under Indomethacin Capsules.

B: Transfer a quantity of finely powdered Capsule contents,equivalent to about 100mg of indomethacin,to a 250-mLflask,add about 100mLof sodium hydroxide solution (1in 2500),shake for 5minutes,and filter.To 1mLof the clear filtrate add 1mLof sodium nitrite solution (1in 1000),mix,and allow to stand for 5minutes.Add 0.5mLof sulfuric acid:a golden yellow color develops.

Test 1: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 1.

Medium: pH6.2phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions);750mL.

Apparatus 1: 75rpm.

Times: 1hour,2hours,4hours,6hours,12hours,24hours.

Procedure— Determine the amount of Indomethacin dissolved from UVabsorbances at the wavelength of maximum absorbance at about 318nm of filtered portions of the solution under test,diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Indomethacin RSin the same medium.

Tolerances— The percentages of the labeled amount of C19H16ClNO4dissolved at the times specified conform to Acceptance Table 1.

Test 2: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 2.

Medium ,Apparatus,and Procedure—Proceed as directed under Test 1,except to use 900mLof Dissolution medium.

Times: 1hour,2hours,4hours,12hours.

Tolerances— The percentages of the labeled amount of C19H16ClNO4dissolved at the times specified conform to Acceptance Table 1.

Test 3: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 3.

Medium: pH6.8phosphate buffer (see Buffer Solutionsin the section Reagents,Indicators,and Solutions);750mL.

Apparatus and Procedure—Proceed as directed under Test 1.

Times: 1hour,2hours,4hours,6hours,12hours,24hours.

Tolerances— The percentages of the labeled amount of C19H16ClNO4dissolved at the times specified conform to Acceptance Table 1.

Procedure for content uniformity— Transfer the contents of 1Capsule to a 200-mLvolumetric flask,and add 100mLof a mixture of equal volumes of methanol and pH7.5phosphate buffer,prepared by dissolving 17.42g of dibasic potassium phosphate in about 800mLof water,adjusting with phosphoric acid to a pHof 7.5,and diluting with water to 1000mL.Sonicate until the contents are dispersed,dilute with the methanol and pH7.5phosphate buffer mixture (1:1)to volume,mix,and centrifuge.Dilute a portion of the clear solution quantitatively,and stepwise if necessary,with the methanol and pH7.5phosphate buffer mixture (1:1)to obtain a solution containing about 25µg of indomethacin per mL.Concomitantly determine the absorbances of this solution and a Standard solution of USP Indomethacin RS,in the methanol and pH7.5phosphate buffer mixture (1:1)having a known concentration of about 25µg per mL,in 1-cm cells at the wavelength of maximum absorbance at about 318nm,with a suitable spectrophotometer,using the methanol and pH7.5phosphate buffer mixture as the blank.Calculate the quantity,in mg,of C19H16ClNO4in the Capsule taken by the formula: in which Tis the labeled quantity,in mg,of indomethacin in the Capsule,Cis the concentration,in µg per mL,of USP Indomethacin RSin the Standard solution,Dis 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 AUand ASare the absorbances of the solution from the Capsule contents and the Standard solution,respectively.

Mobile phase— Prepare a suitable mixture of methanol,water,and phosphoric acid (600:400:0.8),and filter through a membrane filter of 0.5µm or finer porosity.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluted phosphoric acid— Dilute 10mLof phosphoric acid with water to make 1000mLof solution.

Standard indomethacin preparation— Transfer about 40mg of USP Indomethacin RS,accurately weighed,to a 50-mLvolumetric flask,and dissolve in 30mLof acetonitrile.Dilute with Diluted phosphoric acidto volume,and mix.

Standard 4-chlorobenzoic acid preparation— Dissolve a suitable quantity of 4-chlorobenzoic acid,accurately weighed,in acetonitrile to obtain a solution having a known concentration of about 0.18mg per mL.Transfer 1.0mLof this solution to a 50-mLvolumetric flask,dilute with Diluted phosphoric acidto volume,and mix.This solution contains about 3.6µg of 4-chlorobenzoic acid per mL.

Assay preparation— Weigh and finely powder the contents of not less than 20Capsules.Transfer an accurately weighed portion of the powder,equivalent to about 75mg of indomethacin,to a 100-mLvolumetric flask,add 40mLof Diluted phosphoric acid,and shake for 1hour.Sonicate for 15minutes,add 40mLof acetonitrile,mix,sonicate for 15minutes,dilute with acetonitrile to volume,and mix.Centrifuge a portion of this solution,and filter the supernatant through a filter having a porosity of 0.5µm or finer.Use the filtrate as the Assay preparation.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard indomethacin preparation,and record the peak responses as directed under Procedure:the column efficiency determined from the indomethacin peak is not less than 1000theoretical plates,k¢for the indomethacin peak is not less than 4.0,the tailing factor for the indomethacin peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.Chromatograph the Standard 4-chlorobenzoic acid preparation,and record the peak responses as directed under Procedure:k¢for the 4-chlorobenzoic acid peak is not less than 0.9.

Procedure— Separately inject equal volumes (about 20µL)of the Standard indomethacin preparation,the Standard 4-chlorobenzoic acid preparation,and the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,Ca,in mg,of indomethacin in the portion of Capsules taken by the formula: in which Cis the concentration,in mg per mL,of USP Indomethacin RSin the Standard indomethacin preparation,and rUand rSare the indomethacin peak responses obtained from the Assay preparationand the Standard preparation,respectively.Calculate the percentage of 4-chlorobenzoic acid (C7H5ClO2)in the portion of Capsules taken by the formula: in which C4is the concentration,in µg per mL,of 4-chlorobenzoic acid in the Standard 4-chlorobenzoic acid preparation,Cais the quantity,in mg,of indomethacin (C19H16ClNO4)in the portion of Capsule contents taken,determined as directed herein,and rUand rSare the 4-chlorobenzoic acid peak responses obtained from the Assay preparationand the Standard 4-chlorobenzoic acid preparation,respectively:not more than 0.44%is found.