(Ph. Eur. 11.6 update)
Gliclazide Prolonged-release Tablets from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.
Action and use
Inhibition of ATP-dependent potassium channels (sulfonylurea); treatment of diabetes mellitus.
DEFINITION
Gliclazide Prolonged-release Tablets contain Gliclazide. They are formulated so that the medicament is released over a period of several hours.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of Gliclazide. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
Content of gliclazide, C15H21N3O3S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of powdered tablets containing 0.12 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
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Solution A 45 volumes of acetonitrile and 55 volumes of water.
(1) Shake a quantity of the powdered tablets containing 40 mg of Gliclazide for about an hour with 90 mL of acetonitrile. Dilute to 200 mL with water and filter (0.45 μm PTFE is suitable).
(2) Dilute 1 volume of solution (1) to 200 volumes with solution A.
(3) Dissolve 8 mg of gliclazide impurity F BPCRS in 100 mL of solution A. Further dilute 0.5 volumes of this solution to 100 volumes with solution A.
(4) 0.0003% w/v of gliclazide impurity F BPCRS and 0.0001% w/v each of gliclazide BPCRS and gliclazide impurity A BPCRS in solution A.
(5) Dilute 1 volume of solution (2) to 5 volumes with solution A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4 mm) packed with octylsilyl silica gel for chromatography (5 μm) (Licrosorb 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 an autosampler temperature of 4°.
(f) Use a detection wavelength of 235 nm.
(g) Inject 100 μL of each solution.
(h) Allow the chromatography to proceed for twice the retention time of gliclazide.
MOBILE PHASE
0.1 volume of triethylamine, 0.1 volume of trifluoroacetic acid, 40 volumes of acetonitrile and 60 volumes of water.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4):
the resolution between the peaks due to impurity F and gliclazide is at least 1.5;
the resolution between the peak due to impurity A and the preceding negative system peak is at least 1.5.
CALCULATION OF IMPURITIES
For impurity F, use the concentration of impurity F in solution (3).
For all other impurities, use the concentration of gliclazide in solution (2).
For the reporting threshold, use the concentration of gliclazide in solution (5).
For peak identification, use solution (4).
Gliclazide retention time: about 14 minutes.
Relative retention: impurity A, about 0.3; impurity F, about 0.9.
LIMITS
— impurity A: not more than 0.5%;
— impurity F: not more than 0.2%;
— unspecified impurities: for each impurity, not more than 0.2%;
— total impurities: not more than 1.0%;
— reporting threshold: 0.1%.
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in solution A as described under Related substances.
(1) Shake a quantity of the powdered tablets containing 40 mg of Gliclazide for about an hour with 90 mL of acetonitrile. Dilute to 200 mL with water and filter (a 0.45-μm PTFE filter is suitable).
(2) 0.02% w/v of gliclazide BPCRS.
(3) 0.0003% w/v of gliclazide impurity F BPCRS and 0.0001% w/v of gliclazide BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used with the exception of a detection wavelength: use 235 nm for solution (3) and 262 nm for solutions (1) and (2).
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3) at 235 nm, the resolution between impurity F and gliclazide is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of gliclazide, C15H21N3O3S, in the prolonged-release tablets from the chromatograms obtained and using the declared content of C15H21N3O3S in gliclazide BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include A, C, D, E, F and G listed under Gliclazide.
