Hydrocodone Bitartrate Tablets
» Hydrocodone Bitartrate Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of hydrocodone bitartrate disesquihydrate (C18H21NO3·C4H6O6·2½H2O).
Packaging and storage Preserve in tight, light-resistant containers.
Identification Tablets meet the requirements under IdentificationOrganic Nitrogenous Bases 181.
Medium: water; 500 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Phosphate bufferbromothymol blue solution Dissolve 3.40 g of monobasic sodium phosphate in about 50 mL of water, add 18 mL of 0.1 N sodium hydroxide, dilute with water to 500 mL, and mix. Adjust the solution, if necessary, with 1 N sodium hydroxide or 1 N phosphoric acid (Buffer solution) to a pH of 5.8 ± 0.1. Mix 31.2 mg of bromothymol blue with 1.0 mL of 0.1 N sodium hydroxide, add Buffer solution to obtain 500 mL of solution, and mix.
Standard solution Dissolve an accurately weighed quantity of USP Hydrocodone Bitartrate RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 10 µg per mL.
Test solution Pipet into a 125-mL separator a volume of a filtered portion of the solution under test that is estimated to contain about 0.4 mg of hydrocodone bitartrate. Add 2 drops of 6 N ammonium hydroxide, and extract with three 25-mL portions of chloroform. Filter the extracts through about 3 g of anhydrous sodium sulfate supported on filter paper, and combine the filtered extracts in a 100-mL volumetric flask. Add chloroform through the filter to volume, and mix.
Procedure Pipet 10 mL of the Standard solution into a 125-mL separator, and add 25.0 mL of chloroform. Pipet 25 mL of the Test solution into a second 125-mL separator, and add 10.0 mL of water. Pipet 25 mL of chloroform and 10 mL of water into a third 125-mL separator to provide a blank. Treat each mixture as follows. Add 30 mL of Phosphate bufferbromothymol blue solution, and shake vigorously for not less than 15 minutes. Allow the layers to separate, and pass the chloroform layer through filter paper, discarding the first 10 mL of the filtrate. Determine the absorbances of the clear filtrates in 3-cm cells at the wavelength of maximum absorbance at about 415 nm, using the solution from the blank to set the spectrometer. Calculate the amount of C18H21NO3·C4H6O6·2½H2O dissolved by the formula:
(494.49 / 449.46)100(CS / VU)(AU / AS)in which 494.49 and 449.46 are the molecular weights of the hydrated and anhydrous forms of hydrocodone bitartrate, respectively; CS is the concentration, in µg per mL, of USP Hydrocodone Bitartrate RS in the Standard solution; VU is the volume of the filtered solution under test that is estimated to contain 0.4 mg of hydrocodone bitartrate; and AU and AS are the absorbances of the solutions from the Test solution and the Standard solution, respectively.
Tolerances Not less than 75% (Q) of the labeled amount of C18H21NO3·C4H6O6·2½H2O is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Procedure for content uniformity Transfer 1 finely powdered Tablet to a 50-mL volumetric flask, add 0.1 N sulfuric acid to volume, and mix. Filter if necessary, discarding the first 20 mL of the filtrate. Concomitantly determine the absorbances of this solution and a solution of USP Hydrocodone Bitartrate RS in the same medium, having a known concentration of about 100 µg per mL, in 1-cm cells at the wavelength of maximum absorbance at about 280 nm, with a suitable spectrophotometer, using 0.1 N sulfuric acid as the blank. Calculate the quantity, in mg, of C18H21NO3·C4H6O6·2 ½H2O in the Tablet taken by the formula:
(494.49 / 449.46)(TC / D)(AU / AS)in which 494.49 and 449.46 are the molecular weights of the hydrated and anhydrous forms of hydrocodone bitartrate, respectively; T is the labeled quantity, in mg, of hydrocodone bitartrate in the Tablet; C is the concentration, in µg per mL, of USP Hydrocodone Bitartrate RS in the Standard solution; D is the concentration, in µg per mL, of the solution from the Tablet, based upon the labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively.
Assay Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of hydrocodone bitartrate, to a 250-mL separator with the aid of 10 mL of water. Add a small piece of red litmus paper, then add, dropwise, 6 N ammonium hydroxide until the litmus paper turns blue (about 3 drops). Extract with 25-, 25-, 20-, 20-, 15-, and 15-mL portions of chloroform, and filter the chloroform extracts through a small pledget of cotton into a 250-mL conical flask. Evaporate the combined chloroform extracts almost to dryness, remove the flask from the steam bath, and evaporate the remainder of the chloroform with the aid of a current of air. Dissolve the residue in 80 mL of glacial acetic acid, warming, if necessary. Cool, and titrate with 0.02 N perchloric acid VS, determining the endpoint potentiometrically (see Titrimetry 541). Perform a blank determination, and make any necessary correction. Each mL of 0.02 N perchloric acid is equivalent to 9.890 mg of C18H21NO3·C4H6O6·2½H2O.
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USP32NF27 Page 2568Pharmacopeial Forum: Volume No. 27(2) Page 2165