Sulfasalazine Tablets

Sulfonamide aminosalicylate; treatment of ulcerative colitis.

Sulfasalazine Tablets contain Sulfasalazine.

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

95.0 to 105.0% of the stated amount.

A. Shake a quantity of the powdered tablets containing 16 mg of Sulfasalazine with 100 mL of 0.1m sodium hydroxide until dispersed and filter. Dilute 5 mL of the filtrate to 100 mL with a mixture of 7 volumes of water and 2 volumes of 0.1m acetic acid. Record the light absorbance in the range 220 nm to 400 nm, Appendix II B. The absorbances at all wavelengths in the range are similar to those of a solution prepared from sulfasalazine BPCRS in the same manner.

B. In the test for Related substances, the principal peak in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (4).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.1 g of Sulfasalazine with 100 mL of 0.1m ammonia for 30 minutes, centrifuge and use the supernatant liquid. For solution (2) dilute 1 volume of solution (1) to 100 volumes with 0.1m ammonia. Solution (3) contains 0.001% w/v of sulfasalazine derivative for resolution EPCRS in solution (2). Solution (4) contains 0.001% w/v of sulfasalazine BPCRS in 0.1m ammonia.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable), (b) as the mobile phase at a flow rate of 1 mL per minute the gradient elution programme described below and (c) a detection wavelength of 320 nm.

Mobile phase A  A solution containing 0.013% w/v of sodium dihydrogen orthophosphate and 0.25% w/v of sodium acetate adjusted to pH 4.8 with glacial acetic acid.

Mobile phase B  Mix 1 volume of mobile phase A with 4 volumes of methanol.

Inject 20 µL of solution (2) and adjust the sensitivity of the detector so that the height of the peak in the chromatogram is at least 50% of the full scale of the recorder. Inject 20 µL of solution (3). The test is not valid unless the resolution factor between the peaks corresponding to sulfasalazine and sulfasalazine derivative for resolution is at least 3.0.

Inject 20 µL of each of solutions (1) and (2). When the chromatograms are recorded in the prescribed conditions, the approximate retention times relative to sulfasalazine are: impurity A, 2.00; impurity B, 1.85; impurity C, 0.80; impurity D, 1.90; impurity E, 1.63; impurity F, 0.85; impurity G, 1.39; impurity H, 0.16; impurity I, 0.28.

In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%) and the sum of the areas of any such peaks is not greater than 4 times the area of the peak in the chromatogram obtained with solution (2) (4%). Disregard any peak with a retention time shorter than 6 minutes (corresponding to salicylic acid and sulfapyridine) and any peak with an area less than 0.05 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.1 g of Sulfasalazine with 100 mL of 0.1m ammonia for 30 minutes, centrifuge and use the supernatant liquid. For solution (2) prepare a solution containing 0.05% w/v of salicylic acid and 0.05% w/v of sulfapyridine BPCRS in 0.1m ammonia and dilute 1 volume of this solution to 50 volumes with 0.1m ammonia.

The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable), (b) as the mobile phase with a flow rate of 1 mL per minute a mixture of 70 volumes of mobile phase A described in the test for Related substances and 30 volumes of mobile phase B described in the test for Related substances and (c) a detection wavelength of 300 nm.

Inject 20 µL of solution (2) and adjust the sensitivity so that the height of the principal peaks in the chromatogram obtained is at least 50% of the full scale of the recorder. When the chromatogram is recorded in the prescribed conditions the retention time of salicylic acid is about 6 minutes and that of sulfapyridine, about 7 minutes. The test is not valid unless the resolution factor between the peaks corresponding to salicylic acid and sulfapyridine is at least 2.

Inject 20 µL of each solution and allow the chromatography to proceed for 10 minutes. In the chromatogram obtained with solution (1) the areas of any peaks corresponding to salicylic acid and sulfapyridine are not greater than 0.5 times the areas of the corresponding peaks in the chromatogram obtained with solution (2) (0.5% of each).

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 phosphate buffer prepared by dissolving 6.8 g of potassium dihydrogen orthophosphate and 1.66 g of sodium hydroxide in sufficient water to produce 1000 mL and adjusting the pH to 7.5 with 5m sodium hydroxide if necessary, and rotate the paddle at 50 revolutions per minute. Withdraw a sample of 10 mL of the medium, filter and dilute a suitable volume of the filtrate with the dissolution medium to produce a solution containing 0.005% w/v of Sulfasalazine. Measure the absorbance of this solution, Appendix II B, at 406 nm using dissolution medium in the reference cell. Calculate the total content of C₁₈H₁₄N₄O₅S in the medium from the absorbance of a 0.005% w/v solution of sulfasalazine BPCRS in dissolution medium and using the declared content of C₁₈H₁₄N₄O₅S in sulfasalazine BPCRS.

Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.15 g of Sulfasalazine with about 50 mL of 0.1m sodium hydroxide, add sufficient of the same solvent to produce 100 mL, filter and discard the first 20 mL of filtrate. Dilute 5 mL of the filtrate with 750 mL of water, add 20 mL of 0.1m acetic acid, mix and add sufficient water to produce 1000 mL. Measure the absorbance of this solution at the maximum at 359 nm, Appendix II B. Calculate the content of C₁₈H₁₄N₄O₅S in the tablets from the absorbance of a standard solution prepared in the same manner using 0.15 g of sulfasalazine BPCRS and using the declared content of C₁₈H₁₄N₄O₅S in sulfasalazine BPCRS.

The impurities limited by the requirements of this monograph include those listed in the monograph for Sulfasalazine.