Procainamide Hydrochloride Extended-Release Tablets
» Procainamide Hydrochloride Extended-Release Tablets contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of procainamide hydrochloride (C13H21N3O·HCl).
Packaging and storage— Preserve in tight containers.
Labeling— The labeling indicates the Dissolution Test with which the product complies.
USP Reference standards 11
USP Procainamide Hydrochloride RS Click to View Structure
Identification— It responds to the Thin-Layer Chromatographic Identification Test 201, 5 µL of the stock solution prepared as directed for Assay preparation in the Assay and 5 µL of the Stock standard solution being 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.
Dissolution 711
test 1— If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 1.
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Times: 1, 4, and 6 hours.
Procedure— Determine the amount of C13H21N3O·HCl dissolved from UV absorbances at the wavelength of maximum absorbance at about 224 nm, 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 RS in the same Medium.
Tolerances— The percentage of the labeled amount of C13H21N3O·HCl dissolved at the times specified conforms to Acceptance Table 2.
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 USP Dissolution Test 2.
Medium— Proceed as directed for Method B under Delayed-Release Dosage Forms.
acid stage: 0.1 N hydrochloric acid; 900 mL for 1 hour.
buffer stage: 0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2: 50 rpm, with sinkers.
Times: 1, 4, and 8 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 2.
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 USP Dissolution Test 3.
Medium— Proceed as directed under Test 2.
Apparatus 2: 50 rpm, with sinkers.
Times: 1, 3, 6, and 8 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 2.
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 USP Dissolution Test 4.
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 1: 50 rpm.
Times: 1, 2, 4, 8, and 14 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— The percentages of the labeled amount of C13H21N3O·HCl dissolved at the times specified conform to Acceptance Table 2.
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 USP Dissolution Test 5.
Medium— Proceed as directed for Method B under Delayed-Release Dosage Forms.
acid stage: 0.1 N hydrochloric acid; 1000 mL for 1 hour.
buffer stage: 0.05 M phosphate buffer, pH 7.5; 1000 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2: 50 rpm, with sinkers.
Times: 1, 4, 6, and 8 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— Proceed as directed for Tolerances in Test 2.
for 500 mg 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%
for 750 and 1000 mg 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 USP Dissolution Test 6.
Medium— Proceed as directed for Test 2.
Apparatus 2: 50 rpm.
Times: 1, 4, and 8 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— Proceed as directed for Tolerances in Test 2.
for 250 mg tablets—
Time (hours) Amount dissolved
1 between 30% and 60%
4 between 60% and 90%
8 not less than 80%
for 500 mg tablets—
Time (hours) Amount dissolved
1 between 30% and 50%
4 between 60% and 80%
8 not less than 85%
for 750 mg 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 USP Dissolution Test 8.
Medium— Proceed as directed for Method B under Delayed-Release Dosage Forms.
acid stage: 0.1 N hydrochloric acid; 900 mL for 1 hour.
buffer stage: 0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2: 50 rpm, with sinkers.
Times: 1, 4, 6, and 8 hours.
Procedure— Proceed as directed for Procedure in Test 1.
Tolerances— Proceed as directed for Tolerances in 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 905: meet the requirements.
Assay—
Mobile phase— Prepare a suitable mixture of water, methanol, and triethylamine (140:60:1), adjust with phosphoric acid to a pH of 7.5, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Procainamide Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 0.5 mg per mL (Stock standard solution). Quantitatively dilute an accurately measured volume of this solution with Mobile phase to obtain a solution having a known concentration of about 0.05 mg per mL (Standard preparation).
Assay preparation— Transfer not fewer than 10 Tablets, accurately counted, to a 1000-mL volumetric flask, and add 100 mL of 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 700 mL of methanol, and sonicate for 10 minutes, with occasional shaking. Allow to cool, dilute with methanol to volume, and mix. Filter a portion of this solution, discarding the first 10 mL of the filtrate. Quantitatively dilute an accurately measured volume of the filtrate with Mobile phase to obtain a solution having a concentration of about 0.5 mg of procainamide hydrochloride per mL. Use a portion of this stock solution for the Identification test. Quantitatively dilute another accurately measured volume of the stock solution with Mobile phase to obtain a solution having a concentration of about 0.05 mg per mL (Assay preparation).
Resolution solution— Prepare a solution of p-aminobenzoic acid in Mobile phase containing 0.1 mg per mL. Pipet 10 mL of this solution and 10 mL of the Stock standard into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography) 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 1 mL per 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 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.5 for p-aminobenzoic acid and 1.0 for procainamide. Calculate the quantity, in mg, of procainamide hydrochloride (C13H21N3O·HCl) per Tablet taken by the formula:
(L / D)(C)(rU / rS)
in which L is the labeled quantity, in mg, of procainamide hydrochloride in each Tablet; D is 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; C is the concentration, in mg per mL, of USP Procainamide 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— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
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711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 4423
Pharmacopeial Forum: Volume No. 31(1) Page 178