Dispersible Co-trimoxazole Tablets

General Notices

Dispersible Trimethoprim and Sulfamethoxazole Tablets

Action and use

Dihydrofolate reductase inhibitor + sulfonamide antibacterial.

Definition

Dispersible Co-trimoxazole Tablets contain Trimethoprim and Sulfamethoxazole in the proportions, by weight, 1 part trimethoprim to 5 parts sulfamethoxazole in a suitable dispersible basis.

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

Content of trimethoprim, C14H18N4O3

92.5 to 107.5% of the stated amount of trimethoprim.

Content of sulfamethoxazole, C10H11N3O3S

92.5 to 107.5% of the stated amount of sulfamethoxazole.

Identification

A. Filter the aqueous layer reserved in the Assay for trimethoprim. Add, drop wise, sufficient 2m hydrochloric acid to the filtrate to make it just acidic and extract with 50 mL of ether. Wash the ether layer with 10 mL of water, shake with 5 g of anhydrous sodium sulfate, filter and evaporate the filtrate to dryness using a rotary evaporator. Dissolve the residue in the minimum volume of a 5% w/v solution of sodium carbonate, add 1m hydrochloric acid drop wise until precipitation is complete and filter. Wash the residue sparingly with water and dry at 105°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of sulfamethoxazole (RS 327).
B. To a quantity of the powdered tablets containing 50 mg of trimethoprim add 30 mL of 0.1m sodium hydroxide and extract with two 50 mL quantities of chloroform. Wash the combined chloroform extracts with two 10 mL quantities of 0.1m sodium hydroxide and then with 10 mL of water. Shake with 5 g of anhydrous sodium sulfate, filter and evaporate to dryness using a rotary evaporator. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of trimethoprim (RS 354).
C. Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and a mixture of 100 volumes of chloroform, 10 volumes of methanol and 5 volumes of dimethylformamide as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.4 g of Sulfamethoxazole with 20 mL of methanol and filter. Solution (2) contains 2.0% w/v of sulfamethoxazole BPCRS in methanol. Solution (3) contains 0.4% w/v of trimethoprim BPCRS in methanol. After removal of the plate, allow it to dry in air and spray with dilute potassium iodobismuthate solution. One of the principal spots in the chromatogram obtained with solution (1) corresponds to the spot in the chromatogram obtained with solution (2) and the other corresponds to the spot in the chromatogram obtained with solution (3).

Disintegration

The tablets disintegrate within 2 minutes when examined by the disintegration test for tablets and capsules, Appendix XII A1, but using water at 19° to 21°.

Assay

Weigh and powder 20 tablets.

For trimethoprim

To a quantity of the powder containing 50 mg of Trimethoprim add 30 mL of 0.1m sodium hydroxide and extract with four 50 mL quantities of chloroform, washing each extract with the same two 10 mL quantities of 0.1m sodium hydroxide. Reserve the aqueous layer for test A for Identification. Combine the chloroform extracts and extract with four 50 mL quantities of 1m acetic acid. Wash the combined extracts with four 5 mL quantities of chloroform and dilute the aqueous extracts to 250 mL with 1m acetic acid. To 10 mL of the solution add 10 mL of 1m acetic acid and sufficient water to produce 100 mL and measure the absorbance of the resulting solution at the maximum at 271 nm, Appendix II B. Calculate the content of C14H18N4O3 taking 204 as the value of A(1%, 1 cm) at the maximum at 271 nm.

For sulfamethoxazole

Dissolve, as completely as possible, a quantity of the powder containing 0.5 g of Sulfamethoxazole in 60 mL of water and 10 mL of hydrochloric acid. Add 3 g of potassium bromide, cool in ice and titrate slowly with 0.1m sodium nitrite VS, stirring constantly and determining the end point electrometrically. Each mL of 0.1m sodium nitrite VS is equivalent to 25.33 mg of C10H11N3O3S.