(Official April 1, 2006)

A: The retention time of the chlorpheniramine peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

B: Transfer the contents of 1 Capsule to a 10-mL volumetric flask, add 5 mL of methanol, and insert the stopper into the flask. Sonicate this solution for 10 minutes, dilute with water to volume, mix, and filter. Apply separately 10 µL of this solution and 10 µL of a solution of USP Chlorpheniramine Maleate RS in a mixture of methanol and water (1:1) containing about 1.2 mg per mL to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of ethyl acetate, methanol, and ammonium hydroxide (100:5:5) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, allow the solvent to evaporate, and examine the plate under short-wavelength UV light: the RF value of the principal spot observed in the chromatogram of the solution under test corresponds to that obtained from the Standard solution.

Test 1— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 1.

Medium: water; 500 mL.

Apparatus 1: 100 rpm.

Times: 1.5, 6.0, and 10.0 hours.

Procedure— Determine the amount of C16H19ClN2·C4H4O4 dissolved employing the method set forth in the Assay, using a filtered portion of the solution under test in comparison with a Standard solution having a known concentration of USP Chlorpheniramine Maleate RS in the same medium.

Tolerances— The percentages of the labeled amount of C16H19ClN2·C4H4O4 dissolved at the times specified conform to Acceptable Table 1.

Test 2— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 2. Proceed as directed for Method B under Delayed-Release (Enteric-Coated) Articles—General Drug Release Standard.

Medium— Prepare as directed under Method B, except use 900 mL of media. Operate the apparatus for 1 hour in the Acid Stage and use the acceptance criteria given under Tolerances. Operate the apparatus for 6 hours in the Buffer Stage, except to use 900 mL of simulated intestinal fluid TS without enzyme, and use the acceptance criteria given under Tolerances.

Apparatus 2: 50 rpm.

Times: 1.0 hour, 3.0 hours, 7.0 hours.

Procedure— Proceed as directed in Test 1.

Tolerances— The percentages of the labeled amount of C16H19ClN2·C4H4O4 dissolved at the times specified conform to Acceptance Table 1.

Test 1— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 1.

Medium: water; 500 mL.

Apparatus 1: 100 rpm.

Times: 1.5, 6.0, and 10.0 hours.

Procedure— Determine the amount of C16H19ClN2·C4H4O4 dissolved by employing the method set forth in the Assay, using a filtered portion of the solution under test in comparison with a Standard solution having a known concentration of USP Chlorpheniramine Maleate RS in the same medium.

Tolerances— The percentages of the labeled amount of C16H19ClN2·C4H4O4 dissolved at the times specified conform to Acceptance Table 2.

Test 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. Proceed as directed for Procedure for Method B under Apparatus 1 and Apparatus 2, Delayed-Release Dosage Forms.

Medium— Prepare as directed under Method B, except use 900 mL of media. Operate the apparatus for 1 hour in the Acid Stage and use the acceptance criteria given under Tolerances. Operate the apparatus for 6 hours in the Buffer Stage, except to use 900 mL of simulated intestinal fluid TS without enzyme, and use the acceptance criteria given under Tolerances.

Apparatus 2: 50 rpm.

Times: 1.0 hour, 3.0 hours, 7.0 hours.

Procedure— Proceed as directed in Test 1.

Tolerances— The percentages of the labeled amount of C16H19ClN2·C4H4O4 dissolved at the times specified conform to Acceptance Table 2.

(Official April 1, 2006)

(Official January 1, 2007)

Mobile phase— Dissolve 2.0 g of sodium perchlorate in 350 mL of water. Add 650 mL of methanol and 2.0 mL of triethylamine, and mix. Filter, and degas this solution prior to use. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Chlorpheniramine Maleate RS in dilute hydrochloric acid (1 in 100) to obtain a solution having a known concentration of about 0.12 mg per mL.

Assay preparation— Weigh and mix the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the mixture, equivalent to about 120 mg of chlorpheniramine maleate, to a 200-mL volumetric flask. Add about 100 mL of dilute hydrochloric acid (1 in 100), bring to a boil on a hot plate, and continue boiling moderately for 5 minutes. Cool, dilute with dilute hydrochloric acid (1 in 100) to volume, mix, and filter. Transfer 10.0 mL of the filtrate to a 50-mL volumetric flask, dilute with dilute hydrochloric acid (1 in 100) to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 261-nm detector and a 3.9-mm × 15-cm column that contains 10-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 900 theoretical plates, the tailing factor is not greater than 2.0, and the relative standard deviation for replicate injections is not more than 1.5%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of chlorpheniramine maleate (C16H19ClN2·C4H4O4) in the portion of Capsules taken by the formula: in which C is the concentration, in mg per mL, of USP Chlorpheniramine Maleate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.