STP FOR ROPINIROLE TABLETS

1.0) Description: Visual

2.0)  Average Weight: Check weight of 20 tablets at randomly and calculate the average weight by formula :  wt of 20 tablets (gm) x 1000 / 20. found avg. wt in mg

3.0)   Uniformity of weight:

Weigh 20 tablets selected at random and calculate the average weight. Not more than two of the individual weights deviate from the average weight by more than the percentage shown in table.

Weigh the tablets individually and calculate the percentage of deviation for each tablet. By using formula = (experimental weight – theoretical weight)    x 100

Theoretical weight

 Average weight of tablets Percentage deviation More than 80mg but Less than 250mg 7.5% 250mg or More 5%

4.0)     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).

5.0)      Hardness:

The standard method used for tablet hardness testing is compression testing. The tablet is placed between two jaws that crush the tablet. The machine measures the force applied to the tablet and detects when it fractures. Although compressive force is applied to the tablet, along the diameter of the tablet at right angles to the applied force.

6.0)      Disintegration Time:

Unless otherwise stated in the individual monograph, introduce one tablet into each tube and add a disc to each tube. The assembly is suspended in the liquid medium in a suitable vessel, preferably a 1-litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 15mm below the surface of the liquid, and at its lower point is at least 25mm above the bottom of the beaker. At no time should the top of the basket-rack assembly become submerged. There is a thermostatic arrangement for heating the liquid and maintaining the temperature at 37±2°.

If 1 or 2 tablets fail to disintegrate, repeat the test on 12 additional tablets; not less than 16 of the total of 18 tablets tested disintegrate.

If the tablets adhere to the disc and the preparation under examination fails to comply, repeat the test omitting the disc. The preparation complies with the test if all the tablets in the repeat test disintegrate.

7.0)      Dimension of Tablet:

Length, breadth and thickness are determined by vernier in mm

8.0)      Dissolution:

Medium: 500ml of buffer solution pH 4.0, prepared by dissolving 2.9 g of sodium citrate dehydrate and 3.3 g of anhydrous citric acid in 1000ml of water,

Time: 15 minutes

Speed: 50 rpm

Determine by liquid chromatography

Test solution: Use the filtrate, dilute if necessary with the dissolution medium.

Reference solution: Dissolve a quantity of ropinirole HCL reference standard in dissolution medium and dilute with dissolution medium to obtain a solution having a                                known concentration similar to the expected concentration of the test solution.

Chromatographic system:

• A stainless steel column 7.5cm X3.0mm, packed with octadecysilane bonded to porous silica (5µm),
• Mobile Phase: a mixture of 1 volumes of acetonitrile, 4 volumes of medium
• Flow rate: 0.6ml per minute,
• Spectrophotometer set at 250nm,
• Injection volume: 50µl

Inject the reference solution and the test solution.

1mg of Ropinirole HCl is equivalent to 0.8771 mg of Ropinirole.

Limit: NLT 90% of the stated amount of Ropinirole.

9.0)      Leak test:

The apparatus is used to test for the integrity of packed strips, blisters and Alu-Alu Blister pack containing tablets. Ensure apparatus bath is filled with purified water up to mark indicated and add 0.5% crystal violet solution in water. Samples are placed into the desiccators and the lid is placed in position. The pump starts to produce a vacuum 15inHg inside the desiccators and the vacuum is held for 1 minute. The sample remains at the required vacuum level for given time interval buzzer will sound after time is over and will cut off the vacuum pump. As the package is immersed in a colored dye solution the venting of the desiccators will allow any holes to be penetrated by the dye and the contents of the flexible packaging will also be stained with the same coloring material.

Examine all the strips for any leakage by opening the pockets manually. If anyone pocket shows evidence of leakage, reject the sample, stop the Blister / Strip machine and immediately take corrective action.

10.0)    Related substances:

Determined by liquid chromatography,

Solvent mixture: 80 volumes of a buffer solution prepared by dissolving 5g of sodium lauryl sulphate in 800ml of water, adjusted to pH 6.8 with O.P.A. or Sodium hydroxide and 20 volumes of methanol.

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 5mg of ropinirole HCl to a 50ml volumetric flask, add about 35ml of the solvent mixture, shake for 30 minutes and mix with the aid of ultrasound and dilute to volume with the solvent mixture and filter.

Reference solution (a): A 0.002 per cent w/v solution of ropinirole HCl reference standard in the solvent mixture. Dilute 1ml of this solution to 100ml with the same solvent.

Reference solution (b): A 0.003 per cent w/v solution of ropinirole HCl reference standard and 0.005 per cent w/v of ropinirole impurity B reference standard in the solvent mixture. Dilute 1ml of this solution to 100ml with the same solvent.

Chromatographic system:

• A stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5µm)
• Column temperature:50°
• Mobile phase A: a mixture of 20 volumes of methanol, 80 volumes of a buffer solution prepared by dissolving 1.8g of dibasic potassium phosphate in 1000ml water, adjusted to pH 7.4 with O.P.A.
1. A mixture of 80 volumes of methanol and 20 volumes of a buffer solution prepared by dissolving 1.8 g of dibasic potassium phosphate in 1000ml water, adjusted to pH 7.4 with O.P.A.
• flow rate: 1ml per minute,
• a gradient programme using the conditions given below,
• Spectrophotometer set at 250 nm,
• Injection volume: 100 µl.
 Time (in min.) Mobile phase A ( per cent v/v) Mobile phase B (per cent v/v) 0 85 15 8 85 15 30 30 70 40 10 90 60 10 90 60.1 85 15 65 85 15

 Name Relative retention time Correction factor Monopropyl ropinirole1 0.24 0.91 Ropinirole N-oxide2 0.27 – Cyclopentanylindolinone3 0.55 – Hydroxy ropinirole4 0.64 3.03 Ropinirole impurity B5 0.95 0.71 Ropinirole 1.0 – Ethyl ropinirole 1.2 – Propylidene ropinirole7 1.35 0.62

Inject the reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ropinirole HCl and ropinirole impurity B is not less than 2.0 in the chromatogram obtained with reference solution (b), the tailing factor is not more than 2.0 and the relative standard deviation for replicate injections is not more than 5.0 per cent in the chromatogram obtained with reference solution (a).

Inject the test solution. The area of each peak due to monopropyl ropinirole and ropinirole impurity B is not more than 0.6 per cent, the area of each peak due to ropinirole N-oxide, cyclopentanylindolinone and hydroxyl ropinirole is not more than 0.5 per cent, the area of peak due to propylidene ropinirole is not more than 0.4 per cent, the area of any secondary peak is not more than 0.3 per cent and the sum of areas of all secondary peaks is not more than 2.0 per cent calculated by area normalization.

11.0)    Uniformity of content:

Determine by liquid chromatography.

Solvent mixture: Dissolve 3.85g of ammonium acetate in 1000ml water, adjusted to pH 2.5 with O.P.A.

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

Reference solution (a): A 0.011 per cent w/v solution of ropinirole HCl reference standard in the solvent mixture.

Reference standard (b): A solution containing 0.01 per cent w/v of ropinirole HCl reference standard and 0.00005 per cent w/v of ropinirole impurity B reference standard in the solvent mixture.

Chromatographic system:

• A stainless steel column 25 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 14 volumes of acetonitrile, 6 volumes of methanol and 80 volumes of a solution prepared by dissolving 3.85g of ammonium acetate in 900ml of water, adjusted to pH 2.5 with O.P.A. and diluting to 1000 ml with water,
• flow rate: 1ml per minute,
• Spectrophotometer set at 250 nm,
• Injection volume: 20 µl.

Inject reference solution (a) and the test solution.

Calculate the content of Ropinirole in the tablet.

12.0)    Assay:

Determine by liquid chromatography.

Solvent mixture: Dissolve 3.85g of ammonium acetate in 1000ml water, adjusted to pH 2.5 with O.P.A.

Test solution: Weigh and powder 20 tablets. Weigh a quantity of the powder containing about 5mg of ropinirole to a 50ml volumetric flask, add about 25ml of the solvent mixture, shake for 30 minutes and mix with the aid of ultrasound and dilute tp volume with the solvent mixture and filter.

Reference solution (a): A 0.011 per cent w/v solution of ropinirole HCl reference standard in the solvent mixture.

Reference standard (b): A solution containing 0.01 per cent w/v of ropinirole HCl reference standard and 0.00005 per cent w/v of ropinirole impurity B reference standard in the solvent mixture.

Chromatographic system:

• A stainless steel column 25 cm x 4.6 mm, packed with octylsilane bonded to porous silica (5µm)
• Mobile phase: a mixture of 14 volumes of acetonitrile, 6 volumes of methanol and 80 volumes of a solution prepared by dissolving 3.85g of ammonium acetate in 900ml of water, adjusted to pH 2.5 with O.P.A. and diluting to 1000 ml with water,
• flow rate: 1ml per minute,
• Spectrophotometer set at 250 nm,
• Injection volume: 20 µl.

Inject the reference solution (a) and (b). The test is not valid unless the resolution between the peaks due to ropinirole HCl and ropinirole impurity B is not less than 2.0 in the chromatogram obtained with reference solution (b) and the relative standard deviation for replicate injections is not more than 2.0 per cent in the chromatogram obtained with reference solution (a).

Inject the reference solution (a) and the test solution.

Calculate the content of Ropinirole in the tablets.

Acceptance criteria: 90.0%-110.0%

13.0)    MICROBIOLOGICAL PURITY:

Perform the test according to requirements of IP,

Total aerobic Microbial count (TAMC): NMT 103 CFU/g

Total combined yeasts/Moulds count (TYMC): NMT 102 CFU/g

Pathogens: in 1gm drug.

Escherichia Coli – Should be absent

Pseudomonas aeroginosa – Should be absent

Salmonella – Should be absent

Staphylococcus aureus– Should be absent

Abbreviations:

mg: Miligram

ml: Milileter

inHg: Inch of Mercury

rpm: Rounds per minute

CFU: Colony forming unit

w/v: Weight/volume

HCl: Hydrochloric acid

O.P.A.: orthophosphoric acid