Co-codaprin Tablets

General Notices

Aspirin and Codeine Tablets

Action and use

Opioid analgesic + antipyretic; analgesic; anti-inflammatory.

Definition

Co-codaprin Tablets contain Codeine Phosphate and Aspirin in the proportions, by weight, 1 part to 50 parts.

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

Content of codeine phosphate, C18H21NO3,H3PO4, ½H2O

90.0 to 110.0% of the stated amount.

Content of aspirin, C9H8O4

95.0 to 105.0% of the stated amount.

Identification

A. Boil 1 g of the powdered tablets with 10 mL of 1m sodium hydroxide, cool and filter. Acidify the filtrate with 1m sulfuric acid; a white precipitate is produced. To a solution of the precipitate add iron(iii) chloride solution R1; a deep violet colour is produced.
B. Shake 1 g of the powdered tablets with a mixture of 20 mL of water and 1 mL of 1m sulfuric acid for 5 minutes and filter. Reserve the residue for test C. The filtrate yields the reactions characteristic of phosphates, Appendix VI. Make the remainder of the filtrate alkaline with 5m ammonia, extract with dichloromethane, separate the dichloromethane layer and evaporate the dichloromethane. Place a small quantity of the residue on the surface of a drop of nitric acid; a yellow, but no red, colour is produced.
C. Dissolve 0.1 g of the residue obtained in test B in 1 mL of sulfuric acid, add 0.05 mL of iron(iii) chloride solution R1 or 0.05 mL of ammonium molybdate-sulfuric acid solution and warm gently. A bluish violet colour is produced which changes to red on the addition of 0.05 mL of 2m nitric acid.

TESTS

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules with respect to the content of Aspirin, Appendix XII B1.

test conditions
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 500 mL of pH 4.5 buffer prepared by mixing 29.9 g of sodium acetate and 16.6 mL of glacial acetic acid with sufficient water to produce 10 litres, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 20 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 265 nm, Appendix II B using pH 4.5 buffer in the reference cell.
(2) Measure the absorbance of a suitable solution of aspirin BPCRS using pH 4.5 buffer in the reference cell.
determination of content

Calculate the total content of aspirin, C9H8O4, in the medium from the absorbances obtained and using the declared content of C9H8O4 in aspirin BPCRS.

Foreign alkaloids

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

(1) Shake a quantity of the powdered tablets containing 50 mg of Codeine Phosphate with 50 mL of 0.1m hydrochloric acid, filter and make the filtrate alkaline with 5m sodium hydroxide. Extract with two 40-mL quantities of dichloromethane and 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 and dissolve the residue in 2 mL of dichloromethane.
(2) Dilute 1.5 volumes of solution (1) to 100 volumes with dichloromethane.
(3) Dilute 1 volume of solution (1) to 100 volumes with dichloromethane.
chromatographic conditions
(a) Use as the coating silica gel.
(b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, spray with potassium iodobismuthate solution.
mobile phase

6 volumes of 13.5m ammonia, 30 volumes of cyclohexane and 72 volumes of absolute ethanol.

limits

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%).

Salicylic acid

To a quantity of the powdered tablets containing 0.50 g of Aspirin add 50 mL of dichloromethane and 10 mL of water, shake well and allow to separate. Filter the dichloromethane layer through a dry filter paper and evaporate 10 mL of the filtrate to dryness at room temperature using a rotary evaporator. To the residue add 4 mL of ethanol (96%), stir well, dilute to 100 mL with water at a temperature not exceeding 10°, filter immediately and rapidly transfer 50 mL to a Nessler cylinder. Add 1 mL of freshly prepared ammonium iron(iii) sulfate solution R1, mix and allow to stand for 1 minute. Any violet colour produced is not more intense than that obtained by adding 1 mL of freshly prepared ammonium iron(iii) sulfate solution R1 to a mixture of 3 mL of a freshly prepared 0.050% w/v solution of salicylic acid in ethanol (96%) and sufficient water to produce 50 mL contained in a second Nessler cylinder (3.0%).

Assay

Weigh and powder 20 tablets.

For codeine phosphate

To a quantity of the powder containing 24 mg of Codeine Phosphate add 5 mL of 5m sodium hydroxide and 15 mL of water, shake for 2 minutes and extract with three 50-mL quantities of dichloromethane. Wash each extract with the same 10 mL of water, filter through absorbent cotton previously moistened with dichloromethane and evaporate the combined extracts to about 60 mL on a water bath in a current of air. Cool, add 25 mL of water, 5 mL of acetate buffer pH 2.8 and 5 mL of dimethyl yellow and oracet blue 2R solution and titrate with 0.01m dioctyl sodium sulfosuccinate VS with vigorous swirling until near the end point, then add the titrant drop wise and, after each addition, swirl vigorously, allow to separate and swirl gently for 5 seconds. The end point is indicated by the appearance of a permanent pinkish grey colour in the dichloromethane layer. Repeat the operation without the powdered tablets. The difference between the titrations represents the amount of dioctyl sodium sulfosuccinate required.

Dissolve 40 mg of codeine phosphate BPCRS in 25 mL of water and 5 mL of acetate buffer pH 2.8, add 60 mL of dichloromethane and 5 mL of dimethyl yellow and oracet blue 2R solution, shake well to dissolve the codeine phosphate and carry out the method described above beginning at the words ‘and titrate …’. Calculate the content of C18H21NO3,H3PO4,½H2O using the declared content of C18H21NO3,H3PO4,½H2O in codeine phosphate BPCRS.

For aspirin

To a quantity of the powder containing 0.8 g of Aspirin add 20 mL of water and 2 g of sodium citrate and boil under a reflux condenser for 30 minutes. Cool, wash the condenser with 30 mL of warm water and titrate with 0.5m sodium hydroxide VS using phenolphthalein solution R1 as indicator. Each mL of 0.5m sodium hydroxide VS is equivalent to 45.04 mg of C9H8O4.

Storage

Co-codaprin Tablets should be protected from light.

Labelling

The label states that the tablets contain Aspirin, unless this word appears in the name of the tablets (this requirement does not apply in countries where exclusive proprietary rights in the name Aspirin are claimed).