Procainamide Hydrochloride Extended-Release Tablets
»Procainamide Hydrochloride Extended-Release Tablets contain not less than 93.0percent and not more than 107.0percent of the labeled amount of C13H21N3O·HCl.
Packaging and storage—
Preserve in tight containers.
Labeling—
The labeling indicates the Drug Release Testwith which the product complies.
Identification—
It responds to the Thin-Layer Chromatographic Identification test á201ñ,5µLof the stock solution prepared as directed for Assay preparationin the Assayand 5µLof the Stock standard solutionbeing applied to the plate,and a solvent system consisting of a mixture of ether,methanol,and ammonium hydroxide (25:5:1)being used to develop the chromatogram.
Drug release á724ñ—
Test 1:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 1.
Medium:
0.1Nhydrochloric acid;900mL.
Apparatus 2:
50rpm.
Times:
1,4,and 6hours.
Procedure—
Determine the amount of C13H21N3O·HCl dissolved from UVabsorbances at the wavelength of maximum absorbance at about 224nm,using filtered portions of the solution under test,diluted with Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Procainamide Hydrochloride RSin the sameMedium.
Tolerances—
The percentage of the labeled amount of C13H21N3O·HCl dissolved is within the range stated at each of the following times.
| Time (hours) | Amount dissolved |
| 1 | between 30%and 60% |
| 4 | between 60%and 90% |
| 6 | not less than 75% |
Test 2:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 2.
Medium:
Proceed as directed forMethod BunderDelayed-Release (Enteric-Coated)Articles.
ACIDSTAGE—
0.1Nhydrochloric acid;900mLfor 1hour.
BUFFERSTAGE—
0.05Mphosphate buffer,pH7.5;900mL(see Buffer Solutions under Reagents,Indicators,and Solutions)for not less than 8hours.
Apparatus 2:
50rpm,with sinkers.
Times:
1,4,and 8hours.
Procedure—
Proceed as directed for Procedurein Test 1.
Tolerances—
Proceed as directed for Interpretationunder Method A,except to employ the criteria in Acceptance Table 1instead of Acceptance Table 3.The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 1.
| Time (hours) | Amount dissolved |
| 1 | between 30%and 60% |
| 4 | between 60%and 90% |
| 8 | not less than 80% |
Test 3:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 3.
Medium:
Proceed as directed under Test 2.
Apparatus 2:
50rpm,with sinkers.
Times:
1,3,6,and 8hours.
Procedure—
Proceed as directed for Procedurein Test 1.
Tolerances—
Proceed as directed for Interpretationunder Method A,except to employ the criteria in Acceptance Table 1instead of Acceptance Table 3.The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 1.
| Time (hours) | Amount dissolved |
| 1 | between 25%and 50% |
| 3 | between 40%and 75% |
| 6 | between 65%and 90% |
| 8 | not less than 80% |
Test 4:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 4.
Medium:
0.1Nhydrochloric acid;900mL.
Apparatus 1:
50rpm.
Times:
1,2,4,8,and 14hours.
Procedure—
Proceed as directed for Procedurein Test 1.
Tolerances—
Proceed as directed for Interpretationunder Method A,except to employ the criteria in Acceptance Table 1.The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 1.
| Time (hours) | Amount dissolved |
| 1 | not more than 30% |
| 2 | between 25%and 45% |
| 4 | between 45%and 75% |
| 8 | between 70%and 90% |
| 14 | not less than 80% |
Test 5:
If the product complies with this test the labeling indicates that the product meets USPDrug Release Test 5.
Medium:
Proceed as directed forMethod BunderDelayed-Release (Enteric-Coated)Articles.
ACIDSTAGE—
0.1Nhydrochloric acid;1000mLfor 1hour.
BUFFERSTAGE—
0.05Mphosphate buffer,pH7.5;1000mL(see Buffer Solutions under Reagents,Indicators,and Solutions)for not less than 8hours.
Apparatus 2:
50rpm,with sinkers.
Times:
1,4,6,and 8hours.
Procedure—
Proceed as directed forProcedure in Test 1.
Tolerances—
Proceed as directed for Tolerancesin Test 2.
FOR500MG TABLETS—
| Time (hours) | Amount dissolved |
| 1 | between 30%and 45% |
| 4 | between 55%and 75% |
| 6 | not less than 65% |
| 8 | not less than 75% |
FOR750AND1000MG TABLETS—
| Time (hours) | Amount dissolved |
| 1 | between 30%and 50% |
| 4 | between 60%and 80% |
| 6 | between 70%and 90% |
| 8 | not less than 75% |
Test 6:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 6.
Medium:
Proceed as directed for Test 2.
Apparatus 2:
50rpm.
Times:
1,4,and 8hours.
Procedure—
Proceed as directed for Procedurein Test 1.
Tolerances—
Proceed as directed for Tolerancesin Test 2.
FOR250MG TABLETS—
| Time (hours) | Amount dissolved |
| 1 | between 30%and 60% |
| 4 | between 60%and 90% |
| 8 | not less than 80% |
FOR500MG TABLETS—
| Time (hours) | Amount dissolved |
| 1 | between 30%and 50% |
| 4 | between 60%and 80% |
| 8 | not less than 85% |
FOR750MG TABLETS—
| Time (hours) | Amount dissolved |
| 1 | between 30%and 50% |
| 4 | between 60%and 80% |
| 8 | not less than 80% |
Test 8:
If the product complies with this test,the labeling indicates that the product meets USPDrug Release Test 8.
Medium:
Proceed as directed forMethod BunderDelayed-Release (Enteric-Coated)Articles.
ACIDSTAGE—
0.1Nhydrochloric acid;900mLfor 1hour.
BUFFERSTAGE—
0.05Mphosphate buffer,pH7.5;900mL(see Buffer Solutionsunder Reagents,Indicators,and Solutions)for not less than 8hours.
Apparatus 2:
50rpm,with sinkers.
Times:
1,4,6,and 8hours.
Procedure—
Proceed as directed for Procedurein Test 1.
Tolerances—
Proceed as directed for Tolerancesin Test 2.
| Time (hours) | Amount dissolved |
| 1 | between 33%and 50% |
| 4 | between 70%and 85% |
| 6 | not less than 80% |
| 8 | not less than 85% |
Uniformity of dosage units á905ñ:
meet the requirements.
Assay—
Mobile phase—
Prepare a suitable mixture of water,methanol,and triethylamine (140:60:1),adjust with phosphoric acid to a pHof 7.5,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Dissolve an accurately weighed quantity of USP Procainamide Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 0.5mg per mL(Stock standard solution).Dilute an accurately measured volume of this solution quantitatively with Mobile phaseto obtain a solution having a known concentration of about 0.05mg per mL(Standard preparation).
Assay preparation—
Transfer not less than 10Tablets,accurately counted,to a 1000-mLvolumetric flask,and add 100mLof a mixture of methanol and methylene chloride (1:1).Place the flask in a 40
sonicator bath,and sonicate,with occasional shaking,until the Tablets have disintegrated completely.Add about 700mLof methanol,and sonicate for 10minutes,with occasional shaking.Allow to cool,dilute with methanol to volume,and mix.Filter a portion of this solution,discarding the first 10mLof the filtrate.Dilute an accurately measured volume of the filtrate quantitatively with Mobile phaseto obtain a solution having a concentration of about 0.5mg of procainamide hydrochloride per mL.Use a portion of this stock solution for the Identificationtest.Dilute another accurately measured volume of the stock solution quantitatively with Mobile phaseto obtain a solution having a concentration of about 0.05mg per mL(Assay preparation).
sonicator bath,and sonicate,with occasional shaking,until the Tablets have disintegrated completely.Add about 700mLof methanol,and sonicate for 10minutes,with occasional shaking.Allow to cool,dilute with methanol to volume,and mix.Filter a portion of this solution,discarding the first 10mLof the filtrate.Dilute an accurately measured volume of the filtrate quantitatively with Mobile phaseto obtain a solution having a concentration of about 0.5mg of procainamide hydrochloride per mL.Use a portion of this stock solution for the Identificationtest.Dilute another accurately measured volume of the stock solution quantitatively with Mobile phaseto obtain a solution having a concentration of about 0.05mg per mL(Assay preparation).
Resolution solution—
Prepare a solution of p-aminobenzoic acid in Mobile phasecontaining 0.1mg per mL.Pipet 10mLof this solution and 10mLof the Stock standard into a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm ×30-cm column that contains 10-µm packing L1.The flow rate is about 1mLper minute.Chromatograph the Resolution solution:the resolution,R,is not less than 2.0.Chromatograph replicate injections of the Standard preparation:the relative standard deviation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.5for p-aminobenzoic acid and 1.0for procainamide.Calculate the quantity,in mg,of C13H21N3O·HCl per Tablet taken by the formula:
(L/D)(C)(rU/rS),
in which Lis the labeled quantity,in mg,of procainamide hydrochloride in each Tablet,Dis the concentration,in mg per mL,of procainamide hydrochloride in the Assay preparation,based on the number of Tablets taken,the labeled quantity per Tablet,and the extent of dilution,Cis the concentration,in mg per mL,of USP Procainamide Hydrochloride RSin the Standard preparation,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1626
Pharmacopeial Forum:Volume No.29(1)Page 109
Phone Number:1-301-816-8305