Tolbutamide Tablets
Action and use
Inhibition of ATP-dependent potassium channels (sulfonylurea); treatment of diabetes mellitus.
Definition
Tolbutamide Tablets contain Tolbutamide.
Content of tolbutamide, C12H18N2O3S
95.0 to 105.0% of the stated amount.
Identification
Extract a quantity of the powdered tablets containing 1 g of Tolbutamide with 10 mL of chloroform, filter, evaporate the filtrate to dryness, scratching the side of the container, if necessary, to induce crystallisation, and dry the residue at 100° to 105° for 30 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of tolbutamide (RS 343).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using as the medium 900 mL of a solution containing 2.04% w/v of disodium hydrogen orthophosphate and 0.135% w/v of potassium dihydrogen orthophosphate and rotating the basket at 100 revolutions per minute. Withdraw a sample of 10 mL of the medium. Measure the absorbance of the filtered sample, suitably diluted if necessary, at the maximum at 228 nm, Appendix II B. Calculate the total content of tolbutamide, C12H18N2O3S, in the medium taking 417 as the value of A(1%, 1 cm) at the maximum at 228 nm.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 2 volumes of anhydrous formic acid, 8 volumes of methanol and 90 volumes of chloroform as the mobile phase. Apply separately to the plate 5 µL of each of solutions (1) and (2) and 10 µL of solution (3). For solution (1) shake a quantity of the powdered tablets containing 0.50 g of Tolbutamide with 10 mL of acetone and filter. Solution (2) contains 0.015% w/v of toluene-p-sulfonamide in acetone. Solution (3) is a mixture of equal volumes of solutions (1) and (2). After removal of the plate, dry it in a current of warm air and heat at 110° for 10 minutes. While still hot, place the plate in a chromatography tank with an evaporating dish containing a 5% w/v solution of potassium permanganate, add an equal volume of hydrochloric acid and close the tank. Leave the plate in the tank for 2 minutes, then place it in a current of cold air until the excess of chlorine is removed and an area of coating below the line of application gives at most a very faint blue colour with potassium iodide and starch solution; avoid prolonged exposure to cold air. Spray the plate with potassium iodide and starch solution and allow to stand for 5 minutes. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.3%). The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
Assay
Weigh and powder 20 tablets. To a quantity of the powder containing 0.5 g of Tolbutamide add 50 mL of ethanol (96%) previously neutralised to phenolphthalein solution R1, warm to dissolve, add 25 mL of water and titrate with 0.1m sodium hydroxide VS using phenolphthalein solution R1 as indicator. Each mL of 0.1m sodium hydroxide VS is equivalent to 27.03 mg of C12H18N2O3S.