Ropinirole Prolonged-release Tablets

Ropinirole Prolonged-release Tablets manufactured by different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable, as the dissolution profile of the products of different manufactures may not be the same.

Ropinirole Prolonged-release Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of ropinirole, C₁₈H₂₄N₄O.

Usual strengths.  1 mg; 2 mg; 4 mg; 8 mg.

Identification

In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with reference solution (a).

Tests

Dissolution (2.5.2). Complies with the test stated under Tablets.

1 mg of C16H24N2O,HCl is equivalent to 0.8771 mg of C16H24N2O.

Related substances. Determine by liquid chromatography (2.4.14).

Solvent mixture A. A mixture of 80 volumes of acetonitrile and 20 volumes of mobile phase A.
Solvent mixture B. A mixture of 20 volumes of solvent mixture A and 80 volumes of mobile phase A.
Test solution. Weigh and powder 20 tablets. Weigh a quantity of the powdered tablets containing about 5.0 mg of Ropinirole to a 200-ml volumetric flask, add about 100 ml of the solvent mixture A, shake for 30 minutes and mix with the aid of ultrasound and dilute to volume with the same solvent and filter.

Reference solution (a).  A 0.000015 per cent w/v solution of ropinirol hydrochloride RS in solvent mixture B.

Reference solution (b).  A 0.003 per cent w/v solution of ropinirol hydrochloride RS and 0.0001 per cent w/v solution of ropinirole impurity B RS in solvent mixture B.

Reference solution (c).  A 0.0000015 per cent w/v solution of ropinirol hydrochloride RS in solvent mixture B.

Chromatographic system

      –  a stainless steel column 25 cm × 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),

–   column temperature: 40º,

–   mobile phase A. a 0.05 per cent v/v solution of trifluoroacetic acid in water,;

1. B. a mixture of 80 volumes ofacetonitrileand 20 volumes of methanol,

      –  a gradient programme using the conditions given below,

      –  flow rate: 1 ml per minute,

      –  spectrophotometer set at 250 nm,

      –  injection volume: 100 µl.

              Time           Mobile phase A          Mobile phase B

           (in min.)          (per cent v/v)               (per cent v/v)

                  0                          84                                  16

                23                         84                                  16

                36                         40                                  60

               36.1                       84                                  16

                50                         84                                  16

                  

                  

Name                                              Relative          Correction

                                                    retention time          factor

Monopropyl ropinirole¹                  0.42                    1.00               

Ropinirole impurity B²                    0.89                       --

Ropinirole N-hydroxymethyl³       0.94                    1.41

Ropinirole                                         1.00                       --

Ropinirole N-oxide⁴                         1.31                    1.00

Ropinirole methylene dimer⁵         1.82                    1.00

Propylidene ropinirole⁶                   1.96                    0.50

¹  4-[2-(Propylamino)ethyl]indolin-2-one.

²  4-[2-(Dipropylamino)ethyl]indoline-2,3-dione hydrochloride ;

³  4-[2-(Dipropylamino)ethyl]-1-hydroxymethyl)indolin-2-one.

⁴  N-[2-(2-Oxoindolin-4-yl)ethyl]-N-propylpropan-1-amine oxide.

⁵  4-[2-(Dipropylamino)ethyl]-3-({4-[2-(dipropylamino)ethyl]-2-oxo-2,3-dihydro-1H-indol-3-yl}methyl)-2,3-dihydro-1H-indol-2-one

⁶  (Z)-4-[2-(Dipropylamino)ethyl]-3-propylideneindolin-2-one; process impurity included for identification only.

Inject reference solution (a), (b) and (c). The test is not valid unless the resolution between the peaks due to ropinirole and ropinirole impurity B is not less than 2.0, the relative standard deviation for replicate injections is not more than 10.0 per cent for ropinirole impurity B and the signal to noise ratio is not less than 10 obtained with reference solution (c).

Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of each peak corresponding to monopropyl ropinirole, ropinirole impurity B, ropinirole N-hydroxymethyl, ropinirole N-oxide and ropinirole methylene dimer is not more than 0.83 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent),  the area of any other secondary peak is not more than 0.33 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent). The sum of areas of all secondary peaks is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (1.5 per cent). Ignore any peak with an area less than 0.083 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).

Uniformity of content. Determine by liquid chromatography (2.4.14). as described under assay with the following modification.

Test solution. Disperse 1 tablet in the solvent mixture with the aid of ultrasound, and dilute if necessary to obtain a solution having 0.01 per cent w/v solution of  ropinirole.

Inject the test solution and reference solution (a).

Calculate the content of C16H24N2O in the tablets.

Other tests. Comply with the tests stated under Tablets.

Assay. Determine by liquid chromatography (2. 4.14).

Solvent mixture. a mixture of  80 volumes  of acetonitrile, 20 volume of  a solution prepared by dissolving 0.7 ml of orthophosphoric acid in 1000 ml with water,

Test solution. Weigh and powder 20 tablets. Dissolve a quantity of the powdered tablets containing about 5 mg of Ropinirole Hydrochloride to a 50-ml volumetric flask, add about 25 ml of the solvent mixture, shake for 30 minutes and mix with the aid of ultrasound and dilute to 50.0 ml with the  same solvent and filter.

Reference solution (a).  A 0.011 per cent w/v solution of ropinirol hydrochloride RS in solvent mixture.

Reference solution (b).  A 0.01 per cent w/v solution of ropinirol hydrochloride RS and 0.0003 per cent w/v of ropinirole impurity B RS in solvent mixture.

Chromatographic system

     –   a stainless steel column 12.5 cm × 4.6 mm, packed with octylsilane bonded to porous silica (5 µm),

–   column temperature: 40º,

     –   mobile phase: a mixture of  75 volumes  of  methanol and 25 volumes of a buffer solution prepared by dissolving 4.5 g of dibasic sodium phosphate dihydrate in 900 ml of water, adjusted to pH 7.0 with orthophosphoric acid and diluting to 1000 ml with water,

     –   flow rate: 1 ml per minute,

     –   spectrophotometer set at 250 nm,

     –   injection volume: 10 µl.

Inject reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ropinirole hydrochloride and ropinirole impurity B is not less than 2.0, the tailing factor is not more than 1.5 and the relative standard deviation for replicate injections is not more than 1.5 per cent.

Inject reference solution (a) and the test solution.

Calculate the content of C16H24N2O in the tablets.

1 mg of C16H24N2O,HCl is equivalent to 0.8771 mg of C16H24N2O.

Storage. Store protected from moisture, at a temperature below 30⁰.

Labelling. The label states the strength in terms of the equivalent amount of ropinirole.