Codeine Phosphate Tablets
» Codeine Phosphate Tablets contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of C18H21NO3·H3PO4·½H2O.
Packaging and storage— Preserve in well-closed, light-resistant containers.
USP Reference standards 11
USP Codeine Phosphate RS Click to View Structure
Identification—
A: Digest a quantity of finely powdered Tablets, equivalent to about 100 mg of codeine phosphate, with 15 mL of water and 5 mL of 2 N sulfuric acid for 1 hour. Filter, if necessary, and wash any undissolved residue with a few mL of water. Render the filtrate alkaline with 6 N ammonium hydroxide, extract with several small portions of chloroform, and proceed as directed in Identification test A under Codeine Phosphate Injection, beginning with “Evaporate the combined chloroform extracts.” The specified results are observed.
B: To a quantity of finely powdered Tablets, equivalent to about 100 mg of codeine phosphate, add 10 mL of water and 2 drops of 2 N sulfuric acid. Digest, with frequent shaking, for 15 minutes, and filter. Neutralize 5 mL of the filtrate with 6 N ammonium hydroxide, and add silver nitrate TS: a yellow precipitate of silver phosphate is formed, and it is soluble in diluted nitric acid and in 6 N ammonium hydroxide.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure— Determine the amount of C18H21NO3·H3PO4·½H2O dissolved from UV absorbances at the wavelength of maximum absorbance at about 284 nm on 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 Codeine Phosphate RS in the same Medium.
Tolerances— Not less than 75% (Q) of the labeled amount of C18H21NO3·H3PO4·½H2O is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity— Transfer 1 Tablet, previously crushed or finely powdered, to a 50-mL volumetric flask, add 25 mL of water, and shake to dissolve. Dilute with water to volume, and filter, if necessary, discarding the first 20 mL of the filtrate. Transfer an aliquot of the filtrate, equivalent to about 6 mg of codeine phosphate, to a 50-mL volumetric flask containing 2 mL of 3 N hydrochloric acid, and dilute with water to volume. Dissolve an accurately weighed quantity of USP Codeine Phosphate RS in 0.1 N hydrochloric acid, and dilute quantitatively and stepwise with the same solvent to obtain a Standard solution having a known concentration of about 120 µg per mL. Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 284 nm, with a suitable spectrophotometer, using water as the blank. Calculate the quantity, in mg, of C18H21NO3·H3PO4·½H2O in the Tablet taken by the formula:
2.5(C / V)(AU / AS)(406.37 / 397.37)
in which C is the concentration, in µg per mL, of USP Codeine Phosphate RS in the Standard solution; V is the volume, in mL, of the aliquot taken of the solution of the Tablet; AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively; and 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively.
Limit of morphine— A 1-mL portion of the filtrate from Identification test B meets the requirements of the test for Limit of morphine under Codeine Phosphate.
Assay— Weigh and finely powder not fewer than 20 Tablets. Accurately weigh a portion of the powder, equivalent to about 150 mg of codeine phosphate, and transfer to a 100-mL volumetric flask. Add 20 mL of 0.5 N sulfuric acid, and shake the mixture occasionally during 2 hours. Add water to volume, mix, and filter through a filtering crucible. Transfer to a separator an accurately measured portion of the filtrate, equivalent to not less than 75 mg of codeine phosphate, render the solution alkaline with 6 N ammonium hydroxide, and completely extract the alkaloid with successive 15-mL portions of chloroform. Evaporate the combined chloroform solution on a steam bath nearly to dryness. Dissolve the residue in about 2 mL of methanol, heating, if necessary, add methyl red TS, and titrate with 0.02 N sulfuric acid VS to a faint pink color. Add about 40 mL of freshly boiled, cooled water, and complete the titration with 0.02 N sulfuric acid VS. Each mL of 0.02 N sulfuric acid is equivalent to 8.128 mg of C18H21NO3·H3PO4·½H2O.
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Monograph Clydewyn M. Anthony, Ph.D.
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(SM22010) Monographs - Small Molecules 2
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(GCDF2010) General Chapters - Dosage Forms
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