(Ph. Eur. 11.6 update)
Action and use
Inhibition of ATP-dependent potassium channels (sulfonylurea); treatment of diabetes mellitus.
DEFINITION
Gliclazide Tablets contain Gliclazide.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of gliclazide, C15H21N3O3S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 0.16 g of Gliclazide with 20 mL of dichloromethane, centrifuge and evaporate the supernatant liquid to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of gliclazide (RS 168).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Use 900 mL of phosphate buffer pH 7.4, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a 10-mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, expected to contain 0.00125% w/v of Gliclazide at 226 nm and 290 nm, Appendix II B using phosphate buffer pH 7.4 in the reference cell. Correct the absorbance obtained at 226 nm by subtracting the absorbance obtained at 290 nm.
(2) Measure the absorbance of a 0.00124% w/v solution of gliclazide BPCRS using phosphate buffer pH 7.4 in the reference cell. Correct the absorbance obtained at 226 nm by subtracting the absorbance obtained at 290 nm.
DETERMINATION OF CONTENT
Calculate the total content of C15H21N3O3S in the medium from the absorbances obtained and using the declared content of C15H21N3O3S in gliclazide BPCRS.
LIMITS
The amount of gliclazide 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. Prepare the solutions immediately before use.
Solution A: 45 volumes of acetonitrile and 55 volumes of water.
(1) Shake a quantity of the powdered tablets containing 0.8 g of Gliclazide with 160 mL of acetonitrile and dilute to 200 mL with acetonitrile. Filter and dilute 1 volume of the filtrate to 5 volumes with a mixture of 1 volume of acetonitrile and 2
volumes of water.
(2) Dilute 1 volume of solution (1) to 100 volumes with solution A. Further dilute 1 volume to 5 volumes with solution A.
(3) Dissolve 5 mg of gliclazide BPCRS and 15 mg of gliclazide impurity F BPCRS in 25 mL of acetonitrile, dilute to 50 mL with water and dilute 1 volume of the resulting solution to 20 volumes with solution A.
(4) Dissolve 8 mg of gliclazide impurity F BPCRS in 25 mL of acetonitrile, dilute to 50 mL with water and dilute 1 volume of the resulting solution to 100 volumes with solution A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4 mm) packed with octylsilyl silica gel for chromatography (4 μm) (Superspher 60 RP-8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.9 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 235 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1) allow the chromatography to proceed for twice the retention time of the principal peak.
MOBILE PHASE
0.1 volumes of triethylamine, 0.1 volumes of trifluoroacetic acid, 45 volumes of acetonitrile and 55 volumes of water. When the chromatograms are recorded under the prescribed conditions, the relative retention with reference to gliclazide
(retention time about 16 minutes) is: impurity F, about 0.9.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to gliclazide and impurity F is at least 1.8.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity F is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.2%);
the area of any other secondary peak is not greater than the area of the principal in the chromatogram obtained with solution (2) (0.2%).
The total impurity content is not greater than 0.4%.
Disregard any peak with an area less than half 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.
(1) Shake a quantity of the powdered tablets containing 0.8 g of Gliclazide with 160 mL of acetonitrile and dilute to 200 mL with acetonitrile. Filter and dilute 1 volume of the filtrate to 20 volumes with a mixture of 2 volumes of acetonitrile and 3 volumes of water.
(2) Dissolve 40 mg of gliclazide BPCRS in 10 mL of acetonitrile and dilute to 200 mL with a mixture of 2 volumes of acetonitrile and 3 volumes of water.
(3) Dissolve 5 mg of gliclazide BPCRS and 15 mg of gliclazide impurity F BPCRS in 25 mL of acetonitrile, dilute to 50 mL with water and dilute 1 volume of the resulting solution to 20 volumes with a mixture of 45 volumes of acetonitrile and 55 volumes of water.
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 gliclazide and impurity F is at least 1.8.
DETERMINATION OF CONTENT
Calculate the content of C15H21N3O3S in the tablets using the declared content of C15H21N3O3S in gliclazide BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, C, D, E, F and G listed under Gliclazide.
