Indomethacin Suppositories

» Indomethacin Suppositories 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, at controlled room temperature.

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USP Indomethacin RS

Identification—

Standard preparation— Prepare a solution, containing about 125 µg of USP Indomethacin RS per mL, by first dissolving the Reference Standard in a volume of methanol that is one one-hundredth of the volume of the solution to be prepared, then adding ether to volume, and mixing.

Test preparation— Use the ether extract contained in the 200-mL volumetric flask obtained as directed under Assay preparation in the Assay.

Procedure— Separately apply 10 µL each of the Test preparation and the Standard preparation to a thin-layer chromatographic plate (see Chromatography

621

) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the chromatogram in a solvent system consisting of a mixture of chloroform and glacial acetic acid (19:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, air-dry, and examine under short-wavelength UV light: the RF value of the principal spot in the chromatogram of the Test preparation corresponds to that obtained from the Standard preparation.

Dissolution

711

—

Medium: 0.1 M, pH 7.2 phosphate buffer (see Buffer Solutions in the section Reagents, Indicators, and Solutions); 900 mL.

Apparatus 2: 50 rpm.

Time: 60 minutes.

Procedure— Determine the amount of C19H16ClNO4 dissolved from UV absorbances at the wavelength of maximum absorbance at about 320 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 75% (Q) of the labeled amount of C19H16ClNO4 is dissolved in 60 minutes.

Uniformity of dosage units

905

: meet the requirements.

Procedure for content uniformity— Place 1 Suppository into a 100-mL volumetric flask containing 80 mL of a solution of methanol and glacial acetic acid (199:1), shake by mechanical means until the Suppository is dissolved, dilute with the methanol-glacial acetic acid solution to volume, and mix. Filter a portion of the solution, discarding the first 15 mL of the filtrate, and dilute an accurately measured volume of the clear filtrate quantitatively and stepwise, if necessary, with the methanol–glacial acetic acid solution to obtain a solution containing about 25 µg of indomethacin per mL. Concomitantly determine the absorbances of this solution and of a Standard solution of USP Indomethacin RS in the same medium having a known concentration of about 25 µg per mL at the wavelength of maximum absorbance at about 320 nm, with a suitable spectrophotometer, using the methanol–glacial acetic acid solution as the blank. Calculate the quantity, in mg, of C19H16ClNO4 in the Suppository taken by the formula:

(TC / D)(AU / AS)

in which T is the labeled quantity, in mg, of indomethacin in the Suppository; 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 solution from the Suppository, on the basis of the labeled quantity per Suppository and the extent of dilution; and AU and AS are the absorbances of the solution from the Suppository and the Standard solution, respectively.

Assay—

Solvent mixture— Prepare a solution of methanol and glacial acetic acid (199:1).

Standard preparation— Prepare a solution, having a known concentration of about 165 µg of USP Indomethacin RS per mL, by first dissolving an accurately weighed quantity of the Reference Standard in a volume of methanol that is one one-hundredth of the nominal volume of the volumetric flask being used, then adding ether to volume, and mixing. Transfer 15.0 mL of the resulting solution to a 100-mL volumetric flask, dilute with Solvent mixture to volume, and mix to obtain a Standard preparation having a known concentration of about 25 µg of USP Indomethacin RS per mL.

Assay preparation— Weigh, mash, and then mix not less than 10 Suppositories. Transfer an accurately weighed portion of the mass, equivalent to about 25 mg of indomethacin, to a 125-mL separator, add 15 mL of water and 50 mL of ether, and shake until the mass is dissolved. Transfer the ether layer to a 200-mL volumetric flask, extract the aqueous layer with two additional 50-mL portions of ether, and combine the ether extracts in the 200-mL volumetric flask. Discard the aqueous layer. Dilute with Solvent mixture to volume, and mix. Pipet 10 mL of this solution into a 50-mL volumetric flask, dilute with Solvent mixture to volume, and mix.

Procedure— Concomitantly determine the absorbances of the Assay preparation and the Standard preparation at the wavelength of maximum absorbance at about 320 nm, with a suitable spectrophotometer, using Solvent mixture as a blank. Calculate the quantity, in mg, of C19H16ClNO4 in the portion of Suppositories taken by the formula:

C(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.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Clydewyn M. Anthony, Ph.D. Senior Scientific Liaison 1-301-816-8139	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 3499