Diphenhydramine and Pseudoephedrine Capsules
» Diphenhydramine and Pseudoephedrine Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of diphenhydramine hydrochloride (C17H21NO·HCl) and pseudoephedrine hydrochloride (C10H15NO·HCl).
Packaging and storage Preserve in tight containers.
Labeling Label Capsules to state both the contents of the active moieties and the contents of the salts used in formulating the article.
USP Reference standards 11
A: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
B: Developing solventPrepare a mixture of acetonitrile, methylene chloride, and n-propylamine (56:40:4).
Standard solution Dissolve about 12.5 mg of USP Diphenhydramine Hydrochloride RS and 30 mg of USP Pseudoephedrine Hydrochloride RS in 5.0 mL of water in a 50-mL centrifuge tube.
Test solution Transfer an amount of Capsule contents, equivalent to about 12.5 mg of diphenhydramine hydrochloride and about 30.0 mg of pseudoephedrine hydrochloride, to a 50-mL centrifuge tube. Add 5.0 mL of water, and shake.
Procedure To each centrifuge tube add 5.0 mL of a saturated solution of sodium carbonate and 10 mL of methylene chloride. Insert the stoppers into the tubes and shake for about 1 minute. Centrifuge at about 2000 rpm for about 10 minutes until the layers are well separated. Draw off and discard the top layer. Add 5 g of anhydrous sodium sulfate to the remaining solution, insert the stopper tightly, and shake. Separately apply 30 µL (3 × 10 µL) each of the Test solution and the Standard solution to a suitable unactivated thin-layer chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel mixture (see Chromatography 621) and allow the spots to dry. Develop the chromatograms in a paper lined chromatographic chamber equilibrated with the Developing solvent until the solvent front has moved about three-fourths of the length of the plate. Remove the plate, air-dry, place the plate in an iodine chamber, and allow to develop over several hours: the RF values of the principal spots obtained from the Test solution correspond to those obtained from the Standard solution.
Dissolution, Procedure for a Pooled Sample 711
Medium: water, 900 mL.
Apparatus 1: 100 rpm.
Time: 30 minutes.
Procedure Inject a measured volume (about 50 µL) of a filtered portion of the solution under test into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Determine the quantities of C17H21NO·HCl and of C10H15NO·HCl dissolved by employing the procedures set forth in the Assay, making any necessary modifications.
Tolerances Not less than 75% (Q) of the labeled amounts of C17H21NO·HCl and of C10H15NO·HCl are dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Mobile phase Prepare as directed in the Assay.
Diluting solution Prepare a mixture of water, acetonitrile and methanol (64:26:10).
Standard solution Transfer accurately weighed quantities of about 5 mg each of benzhydrol and benzophenone to a 500-mL volumetric flask, dissolve in Diluting solution, using heat and sonication if necessary, dilute with Diluting solution to volume, and mix. Dilute 5.0 mL of this solution quantitatively with Diluting solution to 25.0 mL, mix, and filter.
Test solution Transfer 10 Capsules to a 500-mL volumetric flask, add about 350 mL of Diluting solution, sonicate in warm water at about 40 to effect dissolution, and cool. Dilute with Diluting solution to volume, and mix. Dilute 5.0 mL of this solution with Diluting solution to 25.0 mL, mix, and filter.
Resolution solution Prepare a solution in Diluting solution containing about 2 µg each of benzhydrol and benzophenone, and 100 µg of USP Diphenhydramine Hydrochloride RS, per mL.
Chromatographic system Proceed as directed for Chromatographic system under Assay. Chromatograph 50 µL of the Resolution solution: the resolution, R, between benzhydrol and diphenhydramine is not less than 1.3 and the resolution, R, between diphenhydramine and benzophenone is not less than 2.0.
Procedure Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution, and record the areas of the benzhydrol and benzophenone peaks. Calculate the amounts of benzhydrol and benzophenone in the Capsules taken by the formula:
C(rU / rS)in which C is the concentration of either benzhydrol or benzophenone, in µg per mL, in the Standard solution, and rU and rS are the areas of the corresponding analyte peaks obtained from the Test solution and the Standard solution, respectively: the sum of the amounts of benzhydrol and benzophenone does not exceed 2% (w/w) of the diphenhydramine hydrochloride.
Aqueous solution Dissolve 1.7 g of sodium 1-heptanesulfonate and 0.8 mL of triethylamine in about 800 mL of water, adjust with glacial acetic acid to a pH of 3.3 ± 0.05, dilute with water to 1 L, mix, and filter.
Mobile phase Prepare a filtered and degassed mixture of Aqueous solution, acetonitrile, and methanol (64:26:10). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Transfer about 25 mg of USP Diphenhydramine Hydrochloride RS, accurately weighed, to a 100-mL volumetric flask. Add 25J mg of USP Pseudoephedrine Hydrochloride RS, accurately weighed, J being the ratio of the labeled amount, in mg, of pseudoephedrine hydrochloride to the labeled amount, in mg, of diphenhydramine hydrochloride per capsule, dissolve in 0.5% glacial acetic acid, dilute with 0.5% glacial acetic acid to volume, and mix. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute with 0.5% glacial acetic acid to volume, and mix.
Assay preparation Remove as completely as possible, the contents of not less than 10 Capsules, and weigh accurately. Mix the combined contents, and transfer an accurately weighed portion of the powder, equivalent to about 25 mg of diphenhydramine hydrochloride, to a 100-mL volumetric flask. Dissolve in 0.5% glacial acetic acid, dilute with 0.5% glacial acetic acid to volume, mix, and filter. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute with 0.5% glacial acetic acid to volume, and mix.
Chromatographic system The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the resolution, R, between the pseudoephedrine and diphenhydramine peaks is not less than 3.0. For each analyte peak, the tailing factor is not greater than 2.0, and the relative standard deviation for replicate injections is not greater than 2.0%.
Procedure Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak areas for the two analytes. The relative retention times are about 1.0 for pseudoephedrine and 3.0 for diphenhydramine. Calculate the quantity, in mg, of diphenhydramine hydrochloride (C17H21NO·HCl) in the portion of Capsules taken by formula:
C(rU / rS)in which C is the concentration, in µg per mL, of USP Diphenhydramine Hydrochloride RS in the Standard preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Capsules taken by the same formula changing the terms to refer to pseudoephedrine hydrochloride.
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USP35NF30 Page 2933Pharmacopeial Forum: Volume No. 30(1) Page 98