Codeine Phosphate Tablets, chemical structure, molecular formula, Reference Standards

Codeine Phosphate Tablets

»Codeine Phosphate Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of C18H21NO3·H3PO4·½H2O.

Packaging and storage— Preserve in well-closed,light-resistant containers.

USP Reference standards á11ñ— USP Codeine Phosphate RS.

Identification—

A: Digest a quantity of finely powdered Tablets,equivalent to about 100mg of codeine phosphate,with 15mLof water and 5mLof 2Nsulfuric acid for 1hour.Filter,if necessary,and wash any undissolved residue with a few mLof water.Render the filtrate alkaline with 6Nammonium hydroxide,extract with several small portions of chloroform,and proceed as directed in Identificationtest Aunder 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 100mg of codeine phosphate,add 10mLof water and 2drops of 2Nsulfuric acid.Digest,with frequent shaking,for 15minutes,and filter.Neutralize 5mLof the filtrate with 6Nammonium hydroxide,and add silver nitrate TS:a yellow precipitate of silver phosphate is formed,and it is soluble in diluted nitric acid and in 6Nammonium hydroxide.

Dissolution á711ñ—

Medium: water;900mL.

Apparatus 2: 50rpm.

Time: 45minutes.

Procedure— Determine the amount of C18H21NO3·H3PO4·½H2Odissolved from UVabsorbances at the wavelength of maximum absorbance at about 284nm 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 RSin the same Medium.

Tolerances— Not less than 75%(Q)of the labeled amount of C18H21NO3·H3PO4·½H2Ois dissolved in 45minutes.

Uniformity of dosage units á905ñ: meet the requirements.

Procedure for content uniformity— Transfer 1Tablet,previously crushed or finely powdered,to a 50-mLvolumetric flask,add 25mLof water,and shake to dissolve.Dilute with water to volume,and filter,if necessary,discarding the first 20mLof the filtrate.Transfer an aliquot of the filtrate,equivalent to about 6mg of codeine phosphate,to a 50-mLvolumetric flask containing 2mLof 3Nhydrochloric acid,and dilute with water to volume.Dissolve an accurately weighed quantity of USP Codeine Phosphate RSin 0.1Nhydrochloric acid,and dilute quantitatively and stepwise with the same solvent to obtain a Standard solution having a known concentration of about 120µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 284nm,with a suitable spectrophotometer,using water as the blank.Calculate the quantity,in mg,of C18H21NO3·H3PO4·½H2Oin the Tablet taken by the formula:

2.5(C/V)(AU/AS)(406.37/397.37),

in which Cis the concentration,in µg per mL,of USP Codeine Phosphate RSin the Standard solution;Vis the volume,in mL,of the aliquot taken of the solution of the Tablet;AUand ASare the absorbances of the solution from the Tablet and the Standard solution,respectively;and 406.37and 397.37are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively.

Limit of morphine— A1-mLportion of the filtrate from Identificationtest Bmeets the requirements of the test for Limit of morphineunder Codeine Phosphate.

Assay— Weigh and finely powder not fewer than 20Tablets.Accurately weigh a portion of the powder,equivalent to about 150mg of codeine phosphate,and transfer to a 100-mLvolumetric flask.Add 20mLof 0.5Nsulfuric acid,and shake the mixture occasionally during 2hours.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 75mg of codeine phosphate,render the solution alkaline with 6Nammonium hydroxide,and completely extract the alkaloid with successive 15-mLportions of chloroform.Evaporate the combined chloroform solution on a steam bath nearly to dryness.Dissolve the residue in about 2mLof methanol,heating,if necessary,add methyl red TS,and titrate with 0.02Nsulfuric acid VSto a faint pink color.Add about 40mLof freshly boiled,cooled water,and complete the titration with 0.02Nsulfuric acid VS.Each mLof 0.02Nsulfuric acid is equivalent to 8.128mg of C18H21NO3·H3PO4·½H2O.

Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist

Expert Committee:(PA2)Pharmaceutical Analysis 2

USP28–NF23Page 536

Phone Number:1-301-816-8139