Gliquidone Tablets

General Notices

Action and use

Inhibition of ATP-dependent potassium channels (sulfonylurea); treatment of diabetes mellitus.

Definition

Gliquidone Tablets contain Gliquidone.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of gliquidone, C27H33N3O6S

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 30 mg of Gliquidone in 10 mL of methanol with the aid of ultrasound, filter, evaporate the filtrate to dryness using a rotary evaporator and dry the residue at a temperature of 50° at a pressure of 2 kPa for 1 hour. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of gliquidone (RS 170).
B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of a citro-phosphate buffer prepared by dissolving 35.6 g of disodium hydrogen orthophosphate dihydrate in sufficient water to produce 1000 mL, adjusting the pH to 8.5 with citric acid, and rotate the paddle at 75 revolutions per minute. Withdraw a sample of 50 mL of the medium and filter (Whatman No. 1 filter paper is suitable), discarding the first 15 mL of filtrate. Measure the absorbance of the filtered solution, Appendix II B, at the maximum at 314 nm using a filtered solution of the dissolution medium in the reference cell. Measure the absorbance of a solution of gliquidone BPCRS prepared in the following manner. Dissolve about 30 mg of gliquidone BPCRS in 10 mL of dimethylformamide, add sufficient dissolution medium to produce 100 mL and mix. Dilute 10 mL of this solution to 100 mL with dissolution medium, mix and filter (Whatman No. 1 filter paper is suitable), discarding the first 15 mL of filtrate. Calculate the total content of gliquidone, C27H33N3O6S, in the medium from the absorbances obtained and from the declared content of C27H33N3O6S in gliquidone BPCRS.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel GF254 as the coating substance and a mixture of 5 volumes of glacial acetic acid, 5 volumes of ethanol (96%), 45 volumes of chloroform and 45 volumes of cyclohexane as the mobile phase but allowing the solvent front to ascend 10 cm above the line of application. Apply separately to the plate 10 µL of each of the following five solutions. For solution (1) mix a quantity of the powdered tablets containing 0.1 g of Gliquidone with 8 mL of a mixture of 50 volumes of dichloromethane and 50 volumes of methanol, mix with the aid of ultrasound for 10 minutes, add sufficient of the same solvent mixture to produce 10 mL, filter (Whatman GF/C filter paper is suitable) and use the filtrate. Solution (2) contains 1.0% w/v of gliquidone BPCRS in a mixture of 50 volumes of dichloromethane and 50 volumes of methanol. Solution (3) contains 0.0030% w/v of gliquidone BPCRS in a mixture of 50 volumes of dichloromethane and 50 volumes of methanol. Solution (4) contains 0.010% w/v of gliquidone sulfonamide BPCRS in a mixture of 50 volumes of dichloromethane and 50 volumes of methanol. For solution (5) mix 1 volume of solution (3) and 1 volume of solution (4). After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). In the chromatogram obtained with solution (1) any spot corresponding to gliquidone sulfonamide is not more intense than the spot in the chromatogram obtained with solution (4) (1%) and any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (3) (0.3%). The test is not valid unless the chromatogram obtained with solution (5) shows two clearly separated principal spots.

Assay

Weigh and powder 20 tablets. To a quantity of the powdered tablets containing 0.1 g of Gliquidone add 50 mL of methanol, mix with the aid of ultrasound for 10 minutes, allow to cool, add sufficient methanol to produce 100 mL and filter. Dilute 15 mL of the filtrate to 100 mL with methanol and measure the absorbance of the resulting solution at the maximum at 310 nm, Appendix II B. Calculate the content of C27H33N3O6S in the tablets from the absorbance of a 0.015% w/v solution of gliquidone BPCRS in methanol and using the declared content of C27H33N3O6S in gliquidone BPCRS.