Paracetamol Suppositories

Analgesic; antipyretic.

Paracetamol Suppositories contain Paracetamol in a suitable suppository basis.

The suppositories comply with the requirements stated under Rectal Preparations and with the following requirements.

95.0 to 105.0% of the stated amount.

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

(1) Add sufficient methanol to 1 suppository to produce a final solution containing 0.1% w/v of Paracetamol and warm on a water-bath until the suppository has melted. Allow the solution to cool, with occasional stirring, and filter.

(2) 0.1% w/v of paracetamol BPCRS in methanol.

(a) Use as the coating silica gel GF₂₅₄.

(b) Use the mobile phase as described below.

(c) Apply 10 µL of each solution.

(d) Develop the plate to 15 cm.

(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).

1 volume of methanol and 4 volumes of dichloromethane.

The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

B. Cut into small pieces. To a quantity of the suppositories containing 50 mg of Paracetamol add 1 mL of hydrochloric acid and heat to boiling for 3 minutes; add 10 mL of water and cool. No precipitate is produced. Add 0.05 mL of potassium dichromate solution R1. A violet colour develops which does not change to red.

Carry out the method for liquid chromatography, Appendix III D. Prepare the solutions immediately before use and protect from light.

(1) Cut into small pieces. Dissolve a minimum of 5 suppositories in the minimum volume of ethanol (96%), warming if necessary, and dilute with sufficient water to obtain a solution containing 0.5% w/v of Paracetamol.

(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase and dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.

(3) 0.0005% w/v each of 4-aminophenol and paracetamol BPCRS in the mobile phase.

(4) Dilute a 0.005% w/v solution of 4′-chloroacetanilide in methanol with the mobile phase to produce a solution containing 0.000005% w/v of 4′-chloroacetanilide.

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Zorbax Rx C8 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(c) Use a flow rate of 1.5 mL per minute.

(d) Use a column temperature of 35°.

(e) Use a detection wavelength of 245 nm.

(f) Inject 50 µL of each solution.

(g) For solution (1), allow the chromatography to proceed for 12 times the retention time of the principal peak.

250 volumes of methanol containing 1.15 g of a 40% w/v solution of tetrabutylammonium hydroxide, 375 volumes of 0.05m disodium hydrogen orthophosphate and 375 volumes of 0.05m sodium dihydrogen orthophosphate.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 4.0.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 4-aminophenol is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.1%);

the area of any peak corresponding to 4′-chloroacetanilide is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (10 ppm);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.1%);

the sum of the areas of any other secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Disregard any peak with an area less than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.03%).

To 1 suppository add 30 mL of water and 100 mL of 1m sulfuric acid. Boil under a reflux condenser for 1 hour, cool and add 100 mL of water, 50 g of ice, 50 mL of dilute hydrochloric acid and 0.2 mL of ferroin solution. Titrate with 0.2m ammonium cerium(iv) sulfate VS until a yellow colour is obtained. Each mL of 0.2m ammonium cerium(iv) sulfate VS is equivalent to 15.12 mg of C₈H₉NO₂. Repeat the test using a further 4 suppositories and calculate the average content per suppository from the 5 individual results thus obtained.

To 1 suppository add 10 mL of water and 30 mL of dilute sulfuric acid. Boil under a reflux condenser for 1 hour, cool and add 40 mL of water, 40 g of ice, 15 mL of dilute hydrochloric acid and 0.1 mL of ferroin solution. Titrate with 0.1m ammonium cerium(iv) sulfate VS until a yellow colour is obtained. Each mL of 0.1m ammonium cerium(iv) sulfate VS is equivalent to 7.56 mg of C₈H₉NO₂. Repeat the test using a further 4 suppositories and calculate the average content per suppository from the 5 individual results thus obtained.

To 1 suppository add 10 mL of water and 30 mL of dilute sulfuric acid. Boil under a reflux condenser for 1 hour, cool and add 40 mL of water, 40 g of ice, 15 mL of dilute hydrochloric acid and 0.1 mL of ferroin solution. Titrate with 0.025m ammonium cerium(iv) sulfate VS until a yellow colour is obtained. Each mL of 0.025m ammonium cerium(iv) sulfate VS is equivalent to 1.89 mg of C₈H₉NO₂. Repeat the test using a further 4 suppositories and calculate the average content per suppository from the 5 individual results thus obtained.