Soluble Paracetamol and Caffeine Tablets

Analgesic; antipyretic.

Soluble Paracetamol and Caffeine Tablets contain Paracetamol and Caffeine in either a suitable soluble basis or a suitable soluble, effervescent basis.

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

95.0 to 105.0% of the stated amount.

95.0 to 105.0% of the stated amount.

A. Dissolve, with or without vigorous effervescence as appropriate, on the addition of warm water to produce a slightly opalescent solution.

B. Shake a quantity of the powdered tablets containing 0.5 g of Paracetamol with 20 mL of acetone, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of paracetamol (RS 258).

C. Shake a quantity of the powdered tablets containing 0.1 g of Caffeine with 10 mL of water for 5 minutes, filter and add 10 mL of 1m sodium hydroxide. Extract with three 30-mL quantities of dichloromethane, washing each extract with the same 10 mL of water. Filter the combined extracts through absorbent cotton and evaporate the filtrate to dryness. Dissolve 10 mg of the residue in 1 mL of hydrochloric acid, add 0.1 g of potassium chlorate, evaporate to dryness in a porcelain dish and expose to ammonia vapour. A pink colour is observed.

D. In the Assay for caffeine, the chromatogram obtained with solution (1) shows a principal peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).

Comply with the requirements for Soluble Tablets or with the requirements for Effervescent Tablets, as appropriate.

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

(1) Shake a quantity of the powdered tablets containing 0.5 g of Paracetamol with 50 mL of the mobile phase for 10 minutes and filter.

(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) 0.001% w/v each of 4-aminophenol and paracetamol BPCRS in the mobile phase.

(4) Dilute a 0.01% w/v solution of 4′-chloroacetanilide in methanol with the mobile phase to produce a solution containing 0.00001% 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 peak due to paracetamol in the chromatogram obtained with solution (2) (0.1%);

the total area of any other secondary peaks is not greater than 5 times the area of the peak due to paracetamol in the chromatogram obtained with solution (2) (0.5%).

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.

(1) Shake a quantity of the powdered tablets containing 0.5 mg of Paracetamol with 100 mL of the mobile phase for 10 minutes, dilute to 200 mL with the same solvent, filter through a glass-fibre filter (Whatman GF/C is suitable) and dilute 5 mL of the filtrate to 250 mL with the mobile phase.

(2) 0.005% w/v of paracetamol BPCRS in the mobile phase.

(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 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 an ambient column temperature.

(e) Use a detection wavelength of 243 nm.

(f) Inject 20 µL of each solution.

0.01m sodium pentanesulfonate in a mixture of 22 volumes of methanol and 78 volumes of water, the pH of the solution being adjusted to 2.8 using 2m hydrochloric acid.

Calculate the content of C₈H₉NO₂ in the tablets from the chromatograms obtained and using the declared content of C₈H₉NO₂ in paracetamol BPCRS.

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.

(1) Shake a quantity of the powdered tablets containing 30 mg of Caffeine with 100 mL of the mobile phase for 10 minutes, filter through a glass-fibre filter (Whatman GF/C is suitable) and dilute 5 mL of the filtrate to 50 mL with the mobile phase.

(2) 0.003% w/v of caffeine BPCRS in the mobile phase.

(a) Use a stainless steel column (10 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 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 an ambient column temperature.

(e) Use a detection wavelength of 220 nm.

(f) Inject 20 µL of each solution.

0.01m sodium pentanesulfonate in a mixture of 22 volumes of methanol and 78 volumes of water, the pH of the solution being adjusted to 2.8 using 2m hydrochloric acid.

Calculate the content of C₈H₁₀N₄O₂ in the tablets from the chromatograms obtained and using the declared content of C₈H₁₀N₄O₂ in caffeine BPCRS.

The label states (1) that the tablets should be dissolved in water immediately before use; (2) where applicable, that the tablets are effervescent; (3) the quantities of Paracetamol and Caffeine.