Codeine Phosphate Tablets

General Notices

Action and use

Opioid receptor agonist; analgesic.

Definition

Codeine Phosphate Tablets contain Codeine Phosphate or Codeine Phosphate Sesquihydrate.

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.

Identification

A. Macerate a quantity of the powdered tablets containing 50 mg of codeine phosphate or its equivalent with 5 mL of 1m sulfuric acid and 15 mL of water. Filter, make alkaline with 5m ammonia, extract with successive quantities of chloroform and evaporate the chloroform extracts on a water bath. Place a few mg of the residue, in powder, on the surface of a drop of nitric acid. A yellow but no red colour is produced (distinction from morphine).
B. Heat 10 mg of the residue obtained in test A on a water bath with 1 mL of sulfuric acid and 0.05 mL of iron(iii) chloride solution R1. A blue colour is produced which changes to red on the addition of 0.05 mL of nitric acid.
C. Extract the powdered tablets with water and filter. The filtrate yields reaction B characteristic of phosphates, Appendix VI.

Tests

Foreign alkaloids

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance 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) shake a quantity of the powdered tablets containing 0.25 g of codeine phosphate or its equivalent with 10 mL of a mixture of 4 volumes of 0.01m hydrochloric acid and 1 volume of absolute ethanol for 15 minutes and filter. For solution (2) dilute 1.5 volumes of solution (1) to 100 volumes with a mixture of 4 volumes of 0.01m hydrochloric acid and 1 volume of absolute ethanol. For solution (3) dilute 1 volume of solution (1) to 100 volumes with a mixture of 4 volumes of 0.01m hydrochloric acid and 1 volume of absolute ethanol. After removal of the plate, allow it to dry in air and spray with 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%).

Assay

Weigh and powder 20 tablets. Dissolve a quantity of the powder containing 0.3 g of codeine phosphate or its equivalent as completely as possible in 20 mL of 0.25m sulfuric acid, filter and wash the residue on the filter with 0.25m sulfuric acid until complete extraction of the alkaloid is effected, Appendix XI G. Make alkaline with 5m ammonia and extract with successive quantities of chloroform until complete extraction of the alkaloid is effected. Wash each chloroform solution with the same 10 mL of water and evaporate the chloroform. To the residue add 5 mL of ethanol (96%) previously neutralised to methyl red solution and remove the ethanol by evaporation. Dissolve the residue in 1 mL of neutralised ethanol (96%), add 10 mL of 0.1m hydrochloric acid VS and 10 mL of water and titrate with 0.1m sodium hydroxide VS using methyl red solution as indicator. Each mL of 0.1m hydrochloric acid VS is equivalent to 40.64 mg of C18H21NO3,H3PO4,½H2O.

Storage

Codeine Phosphate Tablets should be protected from light.

Labelling

When the active ingredient is codeine phosphate sesquihydrate, the quantity is stated in terms of the equivalent amount of codeine phosphate.