Gliclazide Tablets

General Notices

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 requirements for Monographs of the British Pharmacopoeia in 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.

determination of content

Calculate the total content of Gliclazide, C₁₅H₂₁N₃O₃S, in the medium from the absorbances obtained and using the declared content of C₁₅H₂₁N₃O₃S, in gliclazide BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare the solutions immediately before use.

(1) Shake a quantity of the powdered tablets containing 0.8 g of Gliclazide for 1 hour with 200 mL of acetonitrile, filter and dilute 10 mL of the filtrate to 50 mL with a mixture of 1 volume of acetonitrile and 2 volumes of water.

(2) Dilute 1 volume of solution (1) to 500 volumes with a mixture of 45 volumes of acetonitrile and 55 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.

(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 a mixture of 45 volumes of acetonitrile and 55 volumes of water.

chromatographic conditions

(a) Use a stainless steel column (25 cm × 4 mm) packed with octylsilyl silica gel for chromatography (4 µm) (Superspher 60RP8 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(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 volume of triethylamine, 0.1 volume of trifluoroacetic acid, 45 volumes of acetonitrile R1 and 55 volumes of water

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to gliclazide and gliclazide impurity F is at least 1.8.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to gliclazide 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 sum of the areas of any other secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (0.4%).

Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

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 for 1 hour with 200 mL of acetonitrile, filter and dilute 10 mL of the filtrate to 200 mL 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.