Disopyramide Phosphate Extended-Release Capsules
»Disopyramide Phosphate Extended-Release Capsules contain an amount of Disopyramide Phosphate equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of disopyramide (C21H29N3O).
Packaging and storage— Preserve in well-closed containers.
Labeling— The labeling indicates the Drug Release Testwith which the product complies.
Identification— Transfer a portion of Capsule contents,equivalent to about 195mg of disopyramide phosphate,to a 25-mLvolumetric flask,add 20mLof methanol,and shake by mechanical means for 20minutes.Dilute with methanol to volume,mix,and filter,discarding the first 10mLof the filtrate.Apply 20µLeach of the subsequent filtrate and of a solution of USP Disopyramide Phosphate RSin methanol containing 7.7mg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with 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 toluene,absolute alcohol,and ammonium hydroxide (170:28:2)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by viewing under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Drug release á724ñ—
Test 1: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 1.
pH2.5,0.1M Phosphate buffer— Dissolve 272g of monobasic potassium phosphate in 20liters of water,and adjust with hydrochloric acid to a pHof 2.50±0.04.[NOTE—Do not adjust back to pH2.50with base if too much acid is added.It is imperative that the ionic strength of the buffer be controlled.]
Medium: pH2.5,0.1M Phosphate buffer;1000mL.
Apparatus 1: 100rpm.
Times: 1hour;2hours;5hours;12hours.
Procedure— Filter 10mLof the solution under test at the required test points.Determine the amount of disopyramide (C21H29N3O)dissolved from UVabsorbances at the wavelength of maximum absorbance at about 261nm of this solution,suitably diluted with Medium,if necessary,using Mediumas the blank,in comparison with a Standard solution having a known concentration of USP Disopyramide Phosphate RSdissolved in Medium.
Tolerances— The percentage of the labeled amount of disopyramide (C21H29N3O)dissolved is within the range stated at each of the following times.
Time (hours) Amount dissolved
1 between 5%and 25%
2 between 17%and 43%
5 between 50%and 80%
12 not less than 85%
Test 2: If the product complies with this test,the labeling indicates that it meets USPDrug Release Test 2.
pH2.5,0.1M Phosphate buffer,and Procedure— Proceed as directed for Test 1.
Medium— Prepare as directed under Test 1;900mL.
Apparatus 2: 100rpm.
Timesand tolerances:
Time (hours) Amount dissolved
1 between 5%and 30%
4 between 40%and 65%
8 between 60%and 90%
12 not less than 75%
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Standard preparation— Dissolve an accurately weighed quantity of USP Disopyramide Phosphate RSin 0.1Nsulfuric acid,and dilute quantitatively and stepwise with the same solvent to obtain a solution having a known concentration of about 40µg per mL.
Assay preparation— Grind the contents of not fewer than 20Capsules to a powder fine enough to pass through a 40-mesh screen.Transfer an accurately weighed portion of the powder,equivalent to about 650mg of disopyramide phosphate,to a 500-mLvolumetric flask.Add about 400mLof 0.1Nsulfuric acid,and shake for 30minutes.Dilute with 0.1Nsulfuric acid to volume,mix,and filter.Dilute an accurately measured portion of the filtrate quantitatively and stepwise with 0.1Nsulfuric acid to obtain a solution having a concentration of about 40µg per mL.
Procedure— Concomitantly determine the absorbances of the Assay preparationand the Standard preparationat the wavelength of maximum absorbance at about 261nm,with a suitable spectrophotometer,using 0.1Nsulfuric acid as the blank.Calculate the quantity,in mg,of C21H29N3Oin the portion of Capsules taken by the formula:
16.25(339.48/437.47)C(AU/AS),
in which 339.48and 437.47are the molecular weights of disopyramide and disopyramide phosphate,respectively;Cis the concentration,in µg per mL,of USP Disopyramide Phosphate RSin the Standard solution;and AUand ASare the absorbances of 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 678
Phone Number:1-301-816-8305