Effervescent Co-codamol Tablets

General Notices

Codeine Phosphate and Paracetamol Effervescent Tablets

Action and use

Opioid analgesic + analgesic; antipyretic.

Definition

Effervescent Co-codamol Tablets contain Codeine Phosphate and Paracetamol in a suitable soluble, effervescent basis.

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

Content of codeine phosphate, C18H21NO3,H3PO4, ½H2O

92.5 to 107.5% of the stated amount.

Content of paracetamol, C8H9NO2

95.0 to 105.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using a TLC silica gel F254 plate (Merck plates are suitable) and a mixture of 1 volume of 13.5m ammonia, 10 volumes of methanol and 90 volumes of dichloromethane as the mobile phase. Apply separately to the plate 10 µL of each of the following solutions. For solution (1) mix a quantity of the powdered tablets containing 24 mg of Codeine Phosphate in 30 mL of water until effervescence ceases, add 10 mL of 1m sodium hydroxide and 30 mL of dichloromethane and shake for 1 minute. Filter the dichloromethane layer through a glass-fibre filter (Whatman GF/C is suitable). Solution (2) contains 0.08% w/v of codeine phosphate BPCRS in methanol (50%). Solution (3) contains 0.08% w/v each of codeine phosphate BPCRS and dihydrocodeine tartrate BPCRS in methanol (50%). After removal of the plate, allow it to dry in air, spray with ethanolic iron(iii) chloride solution and heat at 105° for 10 minutes. The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2). The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots of different colours.
B. In the Assay for codeine phosphate, the chromatogram obtained with solution (2) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (1).

TESTS

4-Aminophenol

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.001% w/v of 4-aminophenol in the mobile phase. For solution (2) stir a quantity of the powdered tablets containing 0.5 g of Paracetamol with 50 mL of the mobile phase for 10 minutes and filter.

The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 is suitable), (b) 0.01m sodium butanesulfonate in a mixture of 0.4 volume of formic acid, 15 volumes of methanol and 85 volumes of water as the mobile phase with a flow rate of 2 mL per minute and (c) a detection wavelength of 272 nm.

In the chromatogram obtained with solution (2) the area of any peak corresponding to 4-aminophenol is not greater than the area of the peak in the chromatogram obtained with solution (1) (0.1%). In the chromatogram obtained with solution (2) peaks with a long retention time may occur due to excipients.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using a TLC silica gel G plate (Analtech plates are suitable) and a mixture of 6 volumes of 13.5m ammonia, 30 volumes of cyclohexane and 72 volumes of absolute ethanol as the mobile phase. Apply separately to the plate 20 µL of each of the following solutions. For solution (1) carefully mix a quantity of the powdered tablets containing 50 mg of Codeine Phosphate with 50 mL of 0.1m hydrochloric acid for 10 minutes and filter. Make the filtrate alkaline with 5m sodium hydroxide and extract with two 40-mL quantities of dichloromethane. Wash the combined extracts with 10 mL of water, filter through a layer of anhydrous sodium sulfate on an absorbent cotton plug moistened with dichloromethane, evaporate the filtrate to dryness at a temperature not exceeding 45° using a rotary evaporator and dissolve the residue in 2 mL of dichloromethane. For solution (2) dilute 1.5 volumes of solution (1) to 100 volumes with dichloromethane. For solution (3) dilute 1 volume of solution (1) to 100 volumes with dichloromethane. After removal of the plate, allow it to dry in air and spray with dilute potassium iodobismuthate solution. Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (1.5%) and not more than one such spot with an Rf value higher than that of the principal spot is more intense than the spot in the chromatogram obtained with solution (3) (1%).

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Codeine Phosphate comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.004% w/v of codeine phosphate BPCRS in the mobile phase. For solution (2) add mobile phase to one tablet and mix with the aid of ultrasound until completely dispersed. Shake for 10 minutes, dilute with sufficient mobile phase to produce a solution containing 0.004% w/v of Codeine Phosphate, filter through a glass-fibre filter (Whatman GF/C is suitable) and use the filtrate.

The chromatographic procedure may be carried out using (a) a stainless steel column (10 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 1.5 mL per minute 0.01m sodium pentanesulfonate in a mixture of 78 volumes of water and 22 volumes of methanol, the pH of the solution being adjusted to 2.8 using 2m hydrochloric acid, and (c) a detection wavelength of 220 nm.

Calculate the content of C18H21NO3,H3PO4, ½H2O in each tablet using the declared content of C18H21NO3,H3PO4, ½H2O in codeine phosphate BPCRS.

Assay

For codeine phosphate

Use the average of the 10 individual results determined in the test for Uniformity of content.

For paracetamol

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) contains 0.005% w/v of paracetamol BPCRS in the mobile phase. For solution (2) mix a quantity of the powdered tablets containing 0.5 g 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.

The chromatographic conditions described under Uniformity of content may be used but with a detection wavelength of 243 nm.

Calculate the content of C8H9NO2 using the declared content of C8H9NO2 in paracetamol BPCRS.

Storage

Effervescent Co-codamol Tablets should be protected from moisture.

Labelling

The label states the quantities of Codeine Phosphate and of Paracetamol in each tablet.

When Co-codamol Effervescent Tablets are prescribed or demanded no strength being stated, tablets containing 8 mg of Codeine Phosphate and 500 mg of Paracetamol shall be dispensed or supplied.