Action and use
Calcium channel blocker.
Definition
Lacidipine Tablets contain Lacidipine. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of lacidipine, C26H33NO6
95.0 to 105.0% of the stated amount.
Carry out all of the following procedures protected from light and prepare solutions immediately before use.
Identification
A. Shake a quantity of whole tablets containing 4 mg of Lacidipine with 50 mL of
absolute ethanol with the aid of ultrasound for 30 minutes. Dilute to 100 mL with
absolute ethanol and filter through a 0.45-µm membrane filter (Millipore Millex is suitable). The
light absorption of the filtrate,
Appendix II B, in the range 250 to 400 nm exhibits maxima only at 284 nm and 368 nm.
B. In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the principal peak in the chromatogram obtained with solution (2).
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 as the medium 500 mL of a solution prepared by mixing 100 mL of
water with 10 mL of
polysorbate 20, shaking gently and diluting to 1000 mL with
water at a temperature of 37°.
procedure
(1) After 45 minutes, withdraw a sample of 10 mL of the medium and filter immediately through a 0.45-µm membrane filter (Millipore Millex is suitable), having first activated the filter with 3 mL of
methanol followed by 5 mL of a 1% w/v solution of
polysorbate 20. Measure the
absorbance of the filtrate in a 2-cm cell, suitably diluted with the dissolution medium if necessary, at the maximum at 284 nm,
Appendix II B, using the dissolution medium in the reference cell.
(2) Measure the
absorbance, in a 2 cm cell, of a solution of
lacidipine BPCRS prepared by diluting a 0.02% w/v solution in
absolute ethanol to a suitable volume with the dissolution medium at the maximum at 284 nm,
Appendix II B, using the dissolution medium in the reference cell.
determination of content
Calculate the total content of lacidipine, C26H33NO6, in the medium using the declared content of C26H33NO6 in lacidipine BPCRS.
Related substances
Carry out method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 20 mg of Lacidipine with 50 mL of
absolute ethanol with the aid of ultrasound for 15 minutes. Cool, dilute to 100 mL with
absolute ethanol, filter through a 0.45-µm membrane filter (Millipore Millex is suitable) and dilute 5 volumes of the filtrate to 20 volumes with
hexane.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Dilute 1 volume of a 0.1% w/v solution of
lacidipine impurity standard BPCRS in
absolute ethanol to 5 volumes with the mobile phase.
chromatographic conditions
(b) Use isocratic elution using the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use ambient column temperature.
(e) Use a detection wavelength of 240 nm.
(f) Inject 20 µL of each solution.
(g) If necessary adjust the composition of the mobile phase so that, in the chromatogram obtained with solution (3), the retention time of the peak due to lacidipine is about 10 minutes.
(h) For solution (1) allow the chromatography to proceed for 2 times the retention time of the principal peak.
mobile phase
system suitability
The test is not valid unless the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with lacidipine impurity standard BPCRS.
limits
In the chromatogram obtained with solution (1):
the area of any peak due to lacidipine impurity B is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (2%, taking into account the correction factor of 0.5);
the area of any other secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the total nominal content of impurities is not greater than 2.5%;
disregard any peak with a relative retention time of 1.5 with respect to the peak due to lacidipine impurity B.
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Lacidipine comply with the requirements stated under Tablets using the following method of analysis. Place one tablet in 50 mL of absolute ethanol, disperse the tablet completely with the aid of ultrasound for 30 minutes crushing with a glass rod if it does not disintegrate, and mix. Cool and filter through a 0.45-µm membrane filter (Millipore Millex is suitable). If necessary further dilute with absolute ethanol to produce a solution containing 0.004% w/v of Lacidipine. Measure the absorbance of the resulting solution at the maximum at 368 nm, Appendix II B, using absolute ethanol in the reference cell. Calculate the content of C26H33NO6 in each tablet from the absorbance obtained from a 0.004% w/v solution of lacidipine BPCRS in absolute ethanol and using the declared content of C26H33NO6 in lacidipine BPCRS.
Assay
Carry out method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse with the aid of ultrasound 10 whole tablets in 50 mL of
absolute ethanol for 10 minutes, cool and filter through a 0.45-µm membrane filter (Millipore Millex is suitable). Dilute a quantity of the filtrate with sufficient mobile phase to produce a solution containing 0.01% w/v of Lacidipine.
(2) Dilute 5 volumes of a 0.04% w/v solution of
lacidipine BPCRS in
absolute ethanol to 20 volumes with the mobile phase.
(3) Dilute 1 volume of a 0.1% w/v solution of
lacidipine impurity standard BPCRS in
absolute ethanol to 5 volumes with the mobile phase.
chromatographic conditions
The chromatographic conditions described under Related substances may be used.
system suitability
The test is not valid unless the chromatogram obtained with solution (3) closely resembles the chromatogram supplied with lacidipine impurity standard BPCRS.
determination of content
Calculate the content of C26H33NO6 in the tablets using the declared content of C26H33NO6 in lacidipine BPCRS.
Storage
Lacidipine Tablets should be protected from light.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Lacidipine.