Levodopa Capsules

General Notices

Action and use

Dopamine precursor; treatment of Parkinson’s disease.

Definition

Levodopa Capsules contain Levodopa.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of levodopa, C₉H₁₁NO₄

95.0 to 105.0% of the stated amount.

Identification

A. Dissolve as completely as possible a quantity of the contents of the capsules containing 0.5 g of Levodopa in 25 mL of 1m hydrochloric acid and filter. Adjust to pH 3 with 5m ammonia, added dropwise with stirring, and allow to stand for several hours, protected from light. Filter, wash the precipitate and dry it at 105°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of levodopa (RS 201).

B. Carry out the method for thin-layer chromatography, Appendix III A, using microcrystalline cellulose as the coating substance and a mixture of 25 volumes of glacial acetic acid, 25 volumes of water and 50 volumes of butan-1-ol as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) shake a quantity of the contents of the capsules containing 0.1 g of Levodopa with 10 mL of 1m hydrochloric acid and filter. Solution (2) contains 1% w/v of levodopa BPCRS in 1m hydrochloric acid. After removal of the plate, dry it in a current of warm air and spray with a freshly prepared mixture of equal volumes of a 10% w/v solution of iron(iii) chloride hexahydrate and a 5% w/v solution of potassium hexacyanoferrate(iii). The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).

C. Shake a quantity of the contents of the capsules containing 20 mg of Levodopa with 5 mL of 0.1m hydrochloric acid. Add 0.1 mL of iron(iii) chloride solution R1; a green colour is produced. To half of the solution add an excess of 5m ammonia; a purple colour is produced. To the remainder of the solution add an excess of 5m sodium hydroxide; a red colour is produced.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of 0.1m hydrochloric acid and rotate the paddle at 50 revolutions per minute. Withdraw a sample of 10 mL of the medium. For capsules containing 0.25 g of Levodopa or less, filter and dilute 2 mL of the filtrate to 10 mL with 0.1m hydrochloric acid. For capsules containing more than 0.25 g of Levodopa, filter and dilute 1 mL of the filtrate to 10 mL with 0.1m hydrochloric acid. Measure the absorbance of the solution, Appendix II B, at 280 nm using 0.1m hydrochloric acid in the reference cell. Calculate the total content of C₉H₁₁NO₄ in the medium taking 142 as the value of A(1%, 1 cm) at the maximum at 280 nm.

Specific optical rotation

–38.5 to –41.5, Appendix V F, when determined in the following manner. Shake a quantity of the contents of the capsules containing 1.25 g of Levodopa with 25 mL of 0.5m hydrochloric acid for 30 minutes, centrifuge and filter the supernatant liquid (Whatman No. 42 filter paper is suitable). To 10 mL of the filtrate add 10 mL of a 21.5% w/v solution of aluminium sulfate, 20 mL of a 21.8% w/v solution of sodium acetate and sufficient water to produce 50 mL and measure the optical rotation. Separately dilute 5 mL of the filtrate to 200 mL with 0.1m hydrochloric acid, mix well and dilute 10 mL to 200 mL with 0.1m hydrochloric acid. Measure the absorbance of the resulting solution at the maximum at 280 nm, Appendix II B. Calculate the content of levodopa, C₉H₁₁NO₄, in the filtrate taking 142 as the value of A(1%, 1 cm) at the maximum at 280 nm and hence calculate the specific optical rotation.

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using a precoated cellulose plate (Merck plates are suitable) and a mixture of 25 volumes of glacial acetic acid, 25 volumes of water and 50 volumes of butan-1-ol as the mobile phase. Apply separately to the plate, as bands 20 mm long, 10 µL of each of solutions (1) and (2) and 20 µL of solution (3) and dry in a current of air. For solution (1) shake a quantity of the contents of the capsules containing 0.1 g of Levodopa with 10 mL of a mixture of equal volumes of anhydrous formic acid and methanol; prepare immediately before use. For solution (2) dilute 1 volume of solution (1) to 200 volumes with methanol. Solution (3) is a mixture of equal volumes of solution (1) and a solution prepared by dissolving 30 mg of l-tyrosine in 1 mL of anhydrous formic acid and diluting to 100 mL with methanol. After removal of the plate, dry it in a current of warm air, spray with a freshly prepared mixture of equal volumes of a 10% w/v solution of iron(iii) chloride hexahydrate and a 5% w/v solution of potassium hexacyanoferrate(iii) and examine the plate immediately. Any secondary band in the chromatogram obtained with solution (1) is not more intense than the band in the chromatogram obtained with solution (2) (0.5%). The test is not valid unless the chromatogram obtained with solution (3) shows a distinct band, at a higher Rf value than the principal band, which is more intense than the band in the chromatogram obtained with solution (2).

Assay

Dissolve as completely as possible a quantity of the mixed contents of 20 capsules containing 0.6 g of Levodopa in 10 mL of anhydrous formic acid, add 80 mL of glacial acetic acid, mix and carry out Method I for non-aqueous titration, Appendix VIII A, using oracet blue 2R solution as indicator. Each mL of 0.1m perchloric acid VS is equivalent to 19.72 mg of C₉H₁₁NO₄.

When l-dopa capsules are prescribed or demanded, Levodopa Capsules shall be dispensed or supplied.