Chlorpropamide Tablets

General Notices

Action and use

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

Definition

Chlorpropamide Tablets contain Chlorpropamide.

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

Content of chlorpropamide, C10H13ClN2O3S

92.5 to 107.5% of the stated amount.

Identification

Extract a quantity of the powdered tablets containing 1 g of Chlorpropamide with five 4-mL quantities of acetone, filter and evaporate the filtrate carefully to dryness on a water-bath. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of chlorpropamide (RS 057).

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 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of a 0.68% w/v solution of potassium dihydrogen orthophosphate adjusted to pH 6.8 by the addition of 1m sodium hydroxide, at a temperature of 37°C, 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, at the maximum at 230 nm, Appendix II B using the medium in the reference cell.
determination of content

Calculate the total content of chlorpropamide, C10H13ClN2O3S, in the medium taking 469 as the value of A(1%, 1 cm) at the maximum at 230 nm.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.5 g of Chlorpropamide with 10 mL of acetone for 10 minutes and filter (Whatman GF/C filter paper is suitable).
(2) 0.015% w/v of 4-chlorobenzenesulfonamide in acetone.
(3) 0.015% w/v of 1,3-dipropylurea in acetone.
(4) Dilute 0.3 volume of solution (1) to 100 volumes with acetone.
(5) Dilute 1 volume of solution (4) to 3 volumes with acetone.
(6) Dissolve 5 mg of 4-chlorobenzenesulfonamide and 5 mg of 1,3-dipropylurea in 2 mL of solution (1) and add sufficient acetone to produce 10 mL.
chromatographic conditions
(a) Use as the coating silica gel 60.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of cold air and heat at 110° for 10 minutes. Place the hot plate in a tank of chlorine gas prepared by the addition of hydrochloric acid to a 5% w/v solution of potassium permanganate contained in a beaker placed in the tank and allow to stand for 2 minutes. Dry it in a current of cold air until the excess of chlorine is removed and an area of the plate below the line of application gives at most a very faint blue colour with a 0.5% w/v solution of potassium iodide in starch mucilage; avoid prolonged exposure to cold air. Spray the plate with a 0.5% w/v solution of potassium iodide in starch mucilage.
mobile phase

11.5 volumes of 13.5m ammonia, 30 volumes of cyclohexane, 50 volumes of methanol and 100 volumes of dichloromethane.

system suitability

The test is not valid unless the chromatogram obtained with solution (6) shows three clearly separated spots with Rf values of approximately 0.4, 0.6 and 0.9 corresponding to chlorpropamide, 4-chlorobenzenesulfonamide and 1,3-dipropylurea, respectively.

limits

In the chromatogram obtained with solution (1):

any spot corresponding to 4-chlorobenzenesulfonamide is not more intense than the spot in the chromatogram obtained with solution (2) (0.3%);

any spot corresponding to 1,3-dipropylurea is not more intense than the spot in the chromatogram obtained with solution (3) (0.3%);

any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (4) (0.3%);

not more than two such spots are more intense than the spot in the chromatogram obtained with solution (5) (0.1%).

Assay

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.25 g of Chlorpropamide with 40 mL of methanol for 20 minutes, add sufficient methanol to produce 50 mL, mix, filter and dilute 5 mL of the filtrate to 100 mL with 0.1m hydrochloric acid. Dilute 10 mL of this solution to 250 mL with 0.1m hydrochloric acid and measure the absorbance of the resulting solution at the maximum at 232 nm, Appendix II B. Calculate the content of C10H13ClN2O3S taking 598 as the value of A(1 cm, 1%) at the maximum at 232 nm.