Pseudoephedrine Hydrochloride Extended-Release Tablets
»Pseudoephedrine Hydrochloride Extended-Release Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of pseudoephedrine hydrochloride (C10H15NO·HCl).
Packaging and storage— Preserve in tight containers.
Labeling— When more than one Drug Releasetest is given,the labeling states the Drug Releasetest used only if Test 1is not used.
Identification—
A:Infrared Absorption á197Kñ—
Test specimen— Triturate a number of Tablets,equivalent to about 180mg of pseudoephedrine hydrochloride,and filter with about 10mLof 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 preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Drug release á724ñ—
FOR PRODUCTS LABELED FOR DOSING EVERY12HOURS—
TEST1—
Medium: water;900mL.
Apparatus 2: 50rpm.
Times: 1,3,and 6hours.
Standard solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RSin water,and dilute quantitatively,and stepwise if necessary,with water to obtain a solution having a known concentration of about 0.13mg per mL.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing the procedure set forth in the Assay.Separately inject equal volumes (about 50µL)of the Standard solutionand 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%
TEST3— If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 3.
Medium,Apparatus,and Times— Proceed as directed for Test 1.
Procedure— Determine the amount of C10H15NO·HCl dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 214nm 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 RSin 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 EVERY24HOURS—
TEST2— If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 2.
Medium: 0.9%sodium chloride in water;50mL.
Apparatus 7: 30cycles per minute;2–3cm amplitude.To prepare the sample,see Figure 1below 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 á724ñ)through netting to secure the Tablet.
  5. Secure netting with HPLCplastic 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 24hours.
Determine the amount of C10H15NO·HCl dissolved by employing the following method.
0.05M Phosphate buffer,pH6.8— Transfer 200mLof water to a 1000-mLvolumetric flask.Add 3.4mLof phosphoric acid and 5mLof triethylamine.Add water to almost 900mL.Adjust with 1Nsodium hydroxide to a pHof about 6.8,dilute with water to volume,and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.05M Phosphate buffer,pH6.8and methanol (9:1).
System suitability solution— Dissolve an accurately weighed quantity of USP Pseudoephedrine RSin water,and dilute quantitatively,and stepwise if necessary,with water to obtain a solution having a known concentration of about 0.4mg per mL.
Standard solutions— Prepare solutions in water having accurately known concentrations of USP Pseudoephedrine Hydrochloride RSin a range around the expected concentration of the solution under test at each time interval.
Chromatographic system (see Chromatography á621ñ)— 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 1.5mLper 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 10µL)of the Standard solutionsand 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%
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of alcohol and ammonium acetate solution (1in 250)(17:3).
Standard preparation— Dissolve an accurately weighed quantity of USP Pseudoephedrine Hydrochloride RSin alcohol to obtain a solution having a known concentration of about 1.2mg per mL.
Assay preparation— Transfer not fewer than 20Tablets to a suitable container,add 500mLof alcohol,and homogenize until the Tablets are dispersed.Quantitatively transfer the contents of the container to a 1000-mLvolumetric flask,dilute with alcohol to volume,mix,and allow to stand for solids to settle.Transfer 25.0mLof the supernatant into a 50-mLvolumetric 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 á621ñ)— 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 0.7mLper 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 10µL)of the Standard preparationand the Assay preparationinto 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 Cis the concentration,in mg per mL,of USP Pseudoephedrine Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 1673
Pharmacopeial Forum:Volume No.29(4)Page 1065
Phone Number:1-301-816-8143