Action and use
Calcium channel blocker.
DEFINITION
Verapamil Tablets contain Verapamil Hydrochloride. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of verapamil hydrochloride, C27H38N2O4,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 0.1 g of Verapamil Hydrochloride with 25 mL of 0.1M hydrochloric acid, filter, extract the filtrate with 25 mL of ether, discard the extract and make the aqueous solution just alkaline with 2M potassium carbonate sesquihydrate. Extract with 25 mL of ether, filter the ether layer through anhydrous sodium sulfate and evaporate to dryness. The infrared absorption spectrum of a thin film of the oily residue, Appendix II A, is concordant with the reference spectrum of verapamil (RS 359).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.01M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 30 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium, if necessary, to produce a solution expected to contain 0.004% w/v of verapamil hydrochloride, at the maximum at 278 nm, Appendix II B, using dissolution medium in the reference cell.
(2) Measure the absorbance of a 0.004% w/v solution of verapamil hydrochloride BPCRS in the dissolution medium using dissolution medium in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of verapamil hydrochloride, C27H38N2O4,HCl in the medium from the absorbances obtained and using the declared content of C27H38N2O4,HCl in verapamil hydrochloride BPCRS.
LIMITS
The amount of verapamil hydrochloride released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Shake a quantity of the powdered tablets containing 0.24 g of Verapamil Hydrochloride with 90 mL of solvent, add sufficient solvent to produce 100 mL, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 50 volumes. Further dilute 1 volume to 10 volumes.
(3) 0.005% w/v of verapamil hydrochloride BPCRS and 0.005% w/v of verapamil impurity I EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 μm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.85 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 278 nm.
(f) Inject 10 μL of each solution.
(g) Allow the chromatography to proceed for 4 times the retention time of verapamil.
MOBILE PHASE
1 volume of 2-heptylamine, 4.7 volumes of glacial acetic acid, 58 volumes of acetonitrile and 137 volumes of 0.01M sodium acetate.
When the chromatograms are recorded under the prescribed conditions, the retention times relative to verapamil (retention time about 6 minutes) are: impurity I, about 0.9 and impurity M, about 2.4.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity I and verapamil is at least 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any such peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%).
Disregard any peak with an area less than half of the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Shake a quantity of the powdered tablets containing 0.24 g of Verapamil Hydrochloride with 90 mL of solvent, add to produce 100 mL and filter. Dilute 1 volume of the filtrate to 20 volumes.
(2) 0.012% w/v of verapamil hydrochloride BPCRS.
(3) 0.005% w/v of verapamil hydrochloride BPCRS and 0.005% w/v of verapamil impurity I EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity I and verapamil is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of verapamil hydrochloride, C27H38N2O4,HCl, in the tablets from the chromatograms obtained and using the declared content of C27H38N2O4,HCl in verapamil hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities D, E, F, G, I, J, K and M listed under Verapamil Hydrochloride.
