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Pseudoephedrine Hydrochloride Extended-Release Tablets
» Pseudoephedrine Hydrochloride Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of pseudoephedrine hydrochloride (C10H15NO·HCl).
Packaging and storage— Preserve in tight containers.
Labeling— When more than one Drug Release test is given, the labeling states the Drug Release test used only if Test 1 is not used.
Labeling— When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
(Official April 1, 2006)
Identification—
A: Infrared Absorption 197K—
Test specimen— Triturate a number of Tablets, equivalent to about 180 mg of pseudoephedrine hydrochloride, and filter with about 10 mL of chloroform collected using vacuum filtration. Maintain the vacuum until no further filtrate can be collected, and evaporate the chloroform on a steam bath, taking care to avoid overheating. Recrystallize the residue from a small amount of dehydrated alcohol.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Drug release 724—
FOR PRODUCTS LABELED FOR DOSING EVERY 12 HOURS—
TEST 1—
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Times: 1, 3, and 6 hours.
Standard solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.13 mg per mL.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing the procedure set forth in the Assay. Separately inject equal volumes (about 50 µL) of the Standard solution and the filtered solution under test. Calculate the amount of C10H15NO·HCl dissolved per Tablet.
Times and Tolerances:
Time (hours) Amount dissolved
1 between 25% and 45%
3 between 50% and 75%
6 not less than 75%
TEST 3— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 3.
Medium, Apparatus, and Times— Proceed as directed for Test 1.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 214 nm on portions of the solution under test, filtered through a 0.45-µm filter and suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Pseudoephedrine Hydrochloride RS in the same Medium.
Times and Tolerances:
Time (hours) Amount dissolved
1 between 25% and 45%
3 between 60% and 80%
6 not less than 80%
FOR PRODUCTS LABELED FOR DOSING EVERY 24 HOURS—
TEST 2— If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 2.
Medium: 0.9% sodium chloride in water; 50 mL.
Apparatus 7: 30 cycles per minute; 2–3 cm amplitude. To prepare the sample, see Figure 1 below that illustrates the following steps:
  1. Place one Tablet on a 5- × 5-cm nylon netting.
  2. Fold netting over the Tablet. Continue folding until the Tablet is enclosed in netting.
  3. Fold netting so that the two open ends meet. The Tablet should be enveloped in the center of the netting.
  4. Insert rod (see Figure 7c under Drug Release 724) through netting to secure the Tablet.
  5. Secure netting with HPLC plastic ferrules or other appropriate device. Trim the excess netting. Attach each sample holder to the vertically reciprocating sample holder.
Click to View Image
Fig. 1
Times: 2, 8, 14, and 24 hours.
Determine the amount of C10H15NO·HCl dissolved by employing the following method.
0.05 M Phosphate buffer, pH 6.8— Transfer 200 mL of water to a 1000-mL volumetric flask. Add 3.4 mL of phosphoric acid and 5 mL of triethylamine. Add water to almost 900 mL. Adjust with 1 N sodium hydroxide to a pH of about 6.8, dilute with water to volume, and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.05 M Phosphate buffer, pH 6.8 and methanol (9:1).
System suitability solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.4 mg per mL.
Standard solutions— Prepare solutions in water having accurately known concentrations of USP Pseudoephedrine Hydrochloride RS in a range around the expected concentration of the solution under test at each time interval.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 5-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 2; 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 solutions and the solution under test into the chromatograph, record the chromatograms, and measure the responses for the major peak. Construct a calibration curve by plotting the peak response versus concentration of the Standard solutions. Determine the amount of C10H15NO·HCl dissolved at each time interval from a linear regression analysis of the calibration curve.
Times and Tolerances:
Time (hours) Amount dissolved
2 between 20% and 35%
8 between 40% and 65%
14 between 60% and 90%
24 not less than 85%
Dissolution 711—
FOR PRODUCTS LABELED FOR DOSING EVERY 12 HOURS—
TEST 1—
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Times: 1, 3, and 6 hours.
Standard solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.13 mg per mL.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing the procedure set forth in the Assay. Separately inject equal volumes (about 50 µL) of the Standard solution and the filtered solution under test. Calculate the amount of C10H15NO·HCl dissolved per Tablet.
Times and Tolerances— The percentage of the labeled amount of C10H15NO·HCl dissolved at the times given conforms to Acceptance Table 2.
Time (hours) Amount dissolved
1 between 25% and 45%
3 between 50% and 75%
6 not less than 75%
TEST 3— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium, Apparatus, and Times— Proceed as directed for Test 1.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing UV absorption at the wavelength of maximum absorbance at about 214 nm on portions of the solution under test, filtered through a 0.45-µm filter and suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Pseudoephedrine Hydrochloride RS in the same Medium.
Times and Tolerances— The percentage of the labeled amount of C10H15NO·HCl dissolved at the times given conforms to Acceptance Table 2.
Time (hours) Amount dissolved
1 between 25% and 45%
3 between 60% and 80%
6 not less than 80%
FOR PRODUCTS LABELED FOR DOSING EVERY 24 HOURS—
TEST 2— If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium: 0.9% sodium chloride in water; 50 mL.
Apparatus 7 (see Drug Release 724): 30 cycles per minute; 2–3 cm amplitude. To prepare the sample, see Figure 1 below that illustrates the following steps:
  1. Place one Tablet on a 5- × 5-cm nylon netting.
  2. Fold netting over the Tablet. Continue folding until the Tablet is enclosed in netting.
  3. Fold netting so that the two open ends meet. The Tablet should be enveloped in the center of the netting.
  4. Insert rod (see Figure 4c under Drug Release 724 ) through netting to secure the Tablet.
  5. Secure netting with HPLC plastic ferrules or other appropriate device. Trim the excess netting. Attach each sample holder to the vertically reciprocating sample holder.
Click to View Image
Fig. 1
Times: 2, 8, 14, and 24 hours.
Determine the amount of C10H15NO·HCl dissolved by employing the following method.
0.05 M Phosphate buffer, pH 6.8— Transfer 200 mL of water to a 1000-mL volumetric flask. Add 3.4 mL of phosphoric acid and 5 mL of triethylamine. Add water to almost 900 mL. Adjust with 1 N sodium hydroxide to a pH of about 6.8, dilute with water to volume, and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.05 M Phosphate buffer, pH 6.8 and methanol (9:1).
System suitability solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.4 mg per mL.
Standard solutions— Prepare solutions in water having accurately known concentrations of USP Pseudoephedrine Hydrochloride RS in a range around the expected concentration of the solution under test at each time interval.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 5-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 2; 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 solutions and the solution under test into the chromatograph, record the chromatograms, and measure the responses for the major peak. Construct a calibration curve by plotting the peak response versus concentration of the Standard solutions. Determine the amount of C10H15NO·HCl dissolved at each time interval from a linear regression analysis of the calibration curve.
Times and Tolerances— The percentage of the labeled amount of C10H15NO·HCl dissolved at the times given conforms to Acceptance Table 2.
Time (hours) Amount dissolved
2 between 20% and 35%
8 between 40% and 65%
14 between 60% and 90%
24 not less than 85%
(Official April 1, 2006)
Uniformity of dosage units 905: meet the requirements.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Mobile phase— Prepare a filtered and degassed mixture of alcohol and ammonium acetate solution (1 in 250) (17:3).
Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RS in alcohol to obtain a solution having a known concentration of about 1.2 mg per mL.
Assay preparation— Transfer not fewer than 20 Tablets to a suitable container, add 500 mL of alcohol, and homogenize until the Tablets are dispersed. Quantitatively transfer the contents of the container to a 1000-mL volumetric flask, dilute with alcohol to volume, mix, and allow to stand for the solids to settle. Transfer 25.0 mL of the supernatant into a 50-mL volumetric flask, dilute with alcohol to volume, and mix. Pass a portion of this solution through a 0.45-µm filter before injection.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains packing L3. The flow rate is about 0.7 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.5; 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 major peaks. Calculate the quantity, in mg, of pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Tablets taken by the formula:
100C(rU / rS),
in which C is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard preparation; and rU and rS are the 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 1858
Pharmacopeial Forum : Volume No. 31(1) Page 182
Phone Number : 1-301-816-8139