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Chlorpheniramine Maleate and Phenylpropanolamine Hydrochloride Extended-Release Capsules
» Chlorpheniramine Maleate and Phenylpropanolamine Hydrochloride Extended-Release Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of chlorpheniramine maleate (C16H19ClN2·C4H4O4) and phenylpropanolamine hydrochloride (C9H13NO·HCl).
Packaging and storage— Preserve in tight, light-resistant containers.
Identification—
A: The retention time of the major peak for chlorpheniramine maleate in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for chlorpheniramine maleate.
B: The retention time of the major peak for phenylpropanolamine hydrochloride in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay for phenylpropanolamine hydrochloride.
Drug release 724
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Times: 3, 6, and 12 hours.
Procedure— Determine the amounts of C16H19ClN2·C4H4O4 and C9H13NO·HCl dissolved by employing the methods set forth in the Assay for chlorpheniramine maleate and the Assay for phenylpropanolamine hydrochloride.
Tolerances— The percentages of the labeled amounts of C16H19 ClN2·C4H4O4 and C9H13NO·HCl dissolved at the specified times conform to Acceptance Table 1.
Time (hours) Amount dissolved
3 between 20% and 50%
6 between 45% and 75%
12 not less than 75%
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Times: 3, 6, and 12 hours.
Procedure— Determine the amounts of C16H19ClN2·C4H4O4 and C9H13NO·HCl dissolved by employing the methods set forth in the Assay for chlorpheniramine maleate and the Assay for phenylpropanolamine hydrochloride.
Tolerances— The percentages of the labeled amounts of C16H19 ClN2·C4H4O4 and C9H13NO·HCl dissolved at the specified times conform to Acceptance Table 2.
Time (hours) Amount dissolved
3 between 20% and 50%
6 between 45% and 75%
12 not less than 75%
(Official April 1, 2006)
Uniformity of dosage units 905: meet the requirements.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay for chlorpheniramine maleate—
Mobile phase— Prepare a filtered and degassed mixture of methanol and water (60:40) containing 0.34 g of monobasic potassium phosphate, 0.05 g of triethylamine hydrochloride, 0.025 g of sodium lauryl sulfate, and 0.1 mL of phosphoric acid in each 100 mL of solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Chlorpheniramine Maleate RS in water to obtain a solution having a known concentration of about 0.8 mg per mL. Quantitatively dilute a portion of this solution with phosphoric acid solution (1 in 1000) to obtain a solution having a known concentration of about 8 µg per mL.
Assay preparation— Transfer not fewer than 10 Capsules to a suitable container, add 100 mL of water and 10 mL of phosphoric acid solution (1 in 20), and heat gently until the Capsules are fully dispersed. Cool to room temperature, and transfer an accurately measured volume of the solution, equivalent to about 0.8 mg of chlorpheniramine maleate, to a 100-mL volumetric flask. Dilute with water to volume, mix, and filter.
System suitability solution— Mix 1 part of the Standard preparation prepared above with 1 part of the Standard preparation prepared as directed in the Assay for phenylpropanolamine hydrochloride.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm × 15-cm column that contains packing L11. The flow rate is about 2 mL per minute. Separately inject about 20 µL of the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between phenylpropanolamine and chlorpheniramine is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the phenylpropanolamine peak is not greater than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the chlorpheniramine peaks. Calculate the quantity, in mg, of chlorpheniramine maleate (C16H19ClN2·C4H4O4) in the portion of Capsules taken by the formula:
100C(rU / rS),
in which C is the concentration, in µg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; and rU and rS are the chlorpheniramine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Assay for phenylpropanolamine hydrochloride—
Mobile phase and Chromatographic system—Proceed as directed in the Assay for chlorpheniramine maleate.
Standard preparation— Dissolve an accurately weighed quantity of USP Phenylpropanolamine Hydrochloride RS in water to obtain a solution having a known concentration of about 2.5 mg per mL. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, add 5 mL of methanol, dilute with phosphoric acid solution (1 in 1000) to volume, and mix.
System suitability solution— Mix 1 part of the Standard preparation prepared above with 1 part of the Standard preparation prepared as directed in the Assay for chlorpheniramine maleate.
Assay preparation— Transfer not fewer than 10 Capsules to a suitable container, add 100 mL of water and 10 mL of phosphoric acid solution (1 in 20), and heat gently until the Capsules are fully dispersed. Cool to room temperature, and transfer an accurately measured volume of the solution, equivalent to about 5 mg of phenylpropanolamine hydrochloride, to a 100-mL volumetric flask. Dilute with water to volume, mix, and filter.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the phenylpropanolamine peaks. Calculate the quantity, in mg, of phenylpropanolamine hydrochloride (C9H13NO·HCl) in the portion of Capsules taken by the formula:
100C(rU / rS),
in which C is the concentration, in mg per mL, of USP Phenylpropanolamine Hydrochloride RS in the Standard preparation; and rU and rS are the phenylpropanolamine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Clydewyn M. Anthony, Ph.D., Scientist
Expert Committee : (MDCCA05) Monograph Development-Cough Cold and Analgesics
USP29–NF24 Page 488
Pharmacopeial Forum : Volume No. 31(1) Page 145
Phone Number : 1-301-816-8139