Codeine Sulfate Tablets
»Codeine Sulfate Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of (C18H21NO3)2·H2SO4·3H2O.
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Digest a quantity of finely powdered Tablets,equivalent to about 50mg of codeine sulfate,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 evaporate the chloroform solution on a steam bath to dryness:the resulting residue of codeine responds to Identificationtest Aunder Codeine.
B: Afiltered solution of Tablets responds to the tests for Sulfate á191ñ.
Dissolution á711ñ—
Medium: water;500mL.
Apparatus 1: 100rpm.
Time: 45minutes.
Procedure— Determine the amount of (C18H21NO3)2·H2SO4·3H2Odissolved from UVabsorbances at the wavelength of maximum absorbance at about 284nm on filtered portions of the solution under test,suitably diluted with water,if necessary,in comparison with a Standard solution having a known concentration of USP Codeine Sulfate RSin the same Medium.
Tolerances— Not less than 75%(Q)of the labeled amount of (C18H21NO3)2·H2SO4·3H2Ois dissolved in 45minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Procedure for content uniformity— Transfer 1Tablet to a 50-mLvolumetric flask.Add 20mLof 0.5Nsulfuric acid and 10mLof water,shake until the Tablet is disintegrated,and allow to stand for 16hours.Dilute with water to volume,and filter,discarding the first few mLof the filtrate.Dilute a portion of the subsequent filtrate quantitatively and stepwise,if necessary,with 0.2Nsulfuric acid to obtain a solution containing approximately 120µg of codeine sulfate (trihydrate)per mL.Concomitantly determine the absorbances of this solution and a Standard solution of USP Codeine Sulfate RSin the same medium having a known concentration of about 110µg per mL,in 1-cm cells,at the wavelength of maximum absorbance at about 284nm,with a suitable spectrophotometer,using 0.2Nsulfuric acid as the blank.Calculate the quantity,in mg,of (C18H21NO3)2·H2SO4·3H2Oin the Tablet taken by the formula:
(750.87/696.82)(TC/D)(AU/AS),
in which 750.87and 696.82are the molecular weights of codeine sulfate trihydrate and anhydrous codeine sulfate,respectively;Tis the labeled quantity,in mg,of codeine sulfate in the Tablet;Cis the concentration,in µg per mL,of USP Codeine Sulfate RSin the Standard solution;Dis the concentration,in µg per mL,of codeine sulfate in the test solution,based upon the labeled quantity per Tablet and the extent of dilution;and AUand ASare the absorbances of the test solution and the Standard solution,respectively.
Assay— Weigh and finely powder not fewer than 20Tablets.Accurately weigh a portion of the powder,equivalent to about 150mg of codeine sulfate,and transfer it completely to a 100-mLvolumetric flask.Add sufficient water to make a thin suspension,then add 20mLof 0.5Nsulfuric acid,shake the mixture occasionally for 2hours,and allow to stand for 16hours.Dilute with water to volume,mix,and filter through a filtering crucible.Transfer an accurately measured portion of the filtrate,equivalent to not less than 75mg of codeine sulfate,to a separator,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,add 25.0mLof 0.02Nsulfuric acid VS,and heat gently to dissolve the codeine and expel all of the chloroform.Cool,add methyl red TS,and titrate the excess acid with 0.02Nsodium hydroxide VS.Each mLof 0.02Nsulfuric acid is equivalent to 7.509mg of (C18H21NO3)2·H2SO4·3H2O.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 537
Phone Number:1-301-816-8139
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