LEVODOPA AND CARBIDOPA TABLETS

Co-careldopa Tablets

Dose: Expressed as levodopa, initially 100 to 125 mg thrice or four times daily after meals, adjusted according to response; usual maintenance dose, 0.75 to 1.5 g daily, in divided doses.

Usual strengths: Expressed in the form x/y where x and y are the strengths, in mg, of anhydrous carbidopa and levodopa respectively as 10/100; 25/100; 25/250.

Labelling: The label states the quantity of Carbidopa, in terms of the equivalent amount of anhydrous carbidopa, and the quantity of Levodopa in each tablet.

Storage: Store in well-closed, light-resistant containers.

STANDARDS

Levodopa and Carbidopa Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of anhydrous carbidopa, C10H14N2O4, and not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of levodopa, C9H11NO4.

Identification: A: In the Assay, the chromatogram obtained with solution (1) shows two principal peaks with the same retention times as those due to carbidopa and levodopa in the chromatogram obtained with solution (2).

B: Shake a quantity of the powdered tablets equivalent to 50 mg of Levodopa with 4 ml of ethanol (95%) and 1 ml of 1M sulphuric acid. Add 2 ml of cinnamaldehyde, allow to stand for 20 minutes, add 50 ml of 0.1M hydrochloric acid, shake for 2 minutes and allow to stand. Filter the aqueous layer and to 5 ml of the filtrate add 0.1 ml of ferric chloride test solution. To half of the solution add an excess of dilute ammonia solution; a purple colour is produced. To the remainder add an excess of sodium hydroxide solution; a deep red colour is produced.

C: Shake a quantity of the powdered tablets equivalent to 1 mg of anhydrous carbidopa with 5 ml of 0.05M sulphuric acid and filter. Add 5 ml of 4-dimethylaminobenzaldehyde solution dimethylaminobenzaldehyde reagent (amendment 4) to the filtrate; a yellow colour is produced.

Uniformity of Content (For tablets containing 10 mg or less of Carbidopa) Comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for high performance liquid chromatography, Appendix 4.3, using the following solutions. For solution (1) shake one tablet with 20 ml of 0.1M phosphoric acid for 30 minutes, add sufficient water to produce 200.0 ml, mix and filter. For solution (2) weigh accurately about 10 mg of carbidopa RS and about 10 mg of methyldopa RS (internal standard), dissolve in 20 ml of 0.1M phosphoric acid by gentle warming and add sufficient water to produce 200.0 ml.

The chromatographic procedure may be carried out as described under Assay.

Calculate the content of C10H14N2O4 in the tablet from the declared content of C10H14N2O4 in carbidopa RS.

Other requirements: Comply with the requirements of tests stated under Tablets.

Assay: Carry out the method for high performance liquid chromatography, Appendix 4.3, using the following solutions. For solution (1) weigh and powder 20 tablets, shake a quantity of the powder equivalent to about 250 mg of Levodopa and 25 mg of Carbidopa, with 50 ml of 0.1M phosphoric acid for 30 minutes, add sufficient water to produce 500.0 ml, mix and filter. For solution (2) weigh accurately about 250 mg of levodopa RS, about 25 mg of carbidopa RS and about 25 mg of methyldopa RS (internal standard), dissolve in 50 ml of 0.1M phosphoric acid by gentle warming and add sufficient water to produce 500.0 ml For solution (2) weigh accurately about 250 mg of levodopa RS and about 25 mg of carbidopa RS, dissolve in 2 ml of 0.1M phosphoric acid by gentle warming and add sufficient water to produce 500.0 ml. (amendment 3).

The chromatographic procedure may be carried out using (a) a stainless steel column (30 cm x 3.9 mm) packed with stationary phase LC2, (b) as mobile phase a solution prepared by mixing 950 ml of sodium dihydrogen phosphate solution (1.162% w/v) with 1.3 ml of sodium 1-decanesulfonate solution (0.024% w/v), adjusting to a pH of about 2.8 with phosphoric acid and diluting with water to produce 1000 ml with a flow rate of about 2 ml per minute and adjusted to obtain retention times of about 4 minutes and 11 minutes for levodopa and carbidopa respectively and (c) a detection wavelength of about 280 nm.

Calculate the content of C10H14N2O4 from the declared content of C10H14N2O4 in carbidopa RS and the content of C9H11NO4 from the declared content of C9H11NO4 in levodopa RS.