Dispersible Co-codaprin Tablets

Dispersible Aspirin and Codeine Tablets

Action and use

Opioid analgesic + antipyretic; analgesic; anti-inflammatory.

Definition

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

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. Effervesce on the addition of water.

B. Boil 1 g of the powdered tablets with 10 mL of 1Msodium hydroxide, cool and filter. Acidify the filtrate with 1Msulfuric acid; a white precipitate is produced. To a solution of the precipitate add iron(iii) chloride solution R1; a deep violet colour is produced.

C. Shake 1 g of the powdered tablets with a mixture of 20 mL of water and 1 mL of 1Msulfuric acid for 5 minutes and filter. Reserve the residue for test D. The filtrate yields the reactions characteristic of phosphates, Appendix VI. Make the remainder of the filtrate alkaline with 5Mammonia, 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.

D. Dissolve 0.1 g of the residue obtained in test C 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 2Mnitric acid.

TEST

Salicylic acid

To a quantity of the powdered tablets containing 0.50 g of Aspirin add 50 mL of dichloromethane and a mixture of 2 mL of 1m hydrochloric acid and 8 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 16 mg of Codeine Phosphate add 20 mL of water and 1 g of disodium edetate, swirl gently until effervescence ceases, shake to dissolve, 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 0.01Mdioctyl 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 complete 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 15 mL of water and swirl until effervescence ceases. Add 5 mL of 0.5m sulfuric acid and extract with 50 mL of ether followed by three 30-mL quantities of ether. Wash the combined extracts with 10 mL of water, filter through absorbent cotton previously moistened with ether, washing the separating funnel and filter with ether. Evaporate the ether in a water bath at 30° in a current of air. Dissolve the residue in 5 mL of acetone and evaporate in a water bath at 30°; again dissolve the residue in 5 mL of acetone and evaporate in a water bath at 30°. Dissolve the residue in 25 mL of ethanol (96%) previously neutralised to phenol red solution and titrate with 0.1m sodium hydroxide VS using phenol red solution as indicator. Each mL of 0.1m sodium hydroxide VS is equivalent to 18.02 mg of C₉H₈O₄.

Storage

Dispersible 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).