Ropinirole Extended-Release Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Ropinirole Extended-Release Tablets contain ropinirole hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ropinirole free base (C₁₆H₂₄N₂O).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: Dissolve 4.5 g of dibasic sodium phosphate dihydrate in 900 mL of water. Adjust with phosphoric acid to a pH of 7.0. Dilute with water to 1 L.

Mobile phase: Methanol and Buffer (75:25)

Dilute phosphoric acid: 0.7 mL phosphoric acid in 1 L of water

Diluent: Acetonitrile and Dilute phosphoric acid (80:20)

System suitability solution:

0.1 mg/mL of USP Ropinirole Hydrochloride RS and 0.003 mg/mL of USP Ropinirole Related Compound B RS in Diluent.

Sonication may be used to aid dissolution.

Standard solution:

0.11 mg/mL of USP Ropinirole Hydrochloride RS in Diluent.

Sonication may be used to aid dissolution.

Sample solution:

Nominally 0.05–0.2 mg/mL of ropinirole prepared as follows:

Transfer NLT 5 Tablets to a suitable volumetric flask containing 75% of the flask volume of Diluent.

Sonicate for NLT 30 min.

Allow to cool to room temperature. Dilute with Diluent to volume.

Pass a portion of the solution through a nylon filter of 0.45-µm pore size and use the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

[For Identification A, use a diode array detector in the range of 200–400 nm.]

Column: 4.6-mm × 12.5-cm; 5-µm packing L7

Column temperature: 40°C

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 1.5 times the retention time of ropinirole

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements:

Resolution: NLT 2.0 between ropinirole related compound B and ropinirole

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation (RSD): NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ropinirole (C₁₆H₂₄N₂O) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (M₁ / M₂) × 100

rᵤ = peak response of ropinirole from the Sample solution

rₛ = peak response of ropinirole from the Standard solution

Cₛ = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of ropinirole in the Sample solution (mg/mL)

M₁ = molecular weight of ropinirole free base = 260.37

M₂ = molecular weight of ropinirole hydrochloride = 296.84

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1

Solution A: 121.2 g/L of trishydroxymethylaminomethane in water

Buffer 1: Dissolve 2.1 g of citric acid monohydrate in 900 mL of water. Adjust with Solution A to a pH of 4.0. Dilute with water to 1 L.

Buffer 2: Dissolve 3.9 g of ammonium acetate in 900 mL of water. Adjust with phosphoric acid to a pH of 2.5. Dilute with water to 1 L.

Medium: Buffer 1; 500 mL. Deaerate as appropriate.

Times: 2, 12, and 24 h

Mobile phase: Acetonitrile, methanol, and Buffer 2 (14:6:80)

Standard solution: (L/400) mg/mL of USP Ropinirole Hydrochloride RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-µm pore size

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 12.5-cm; 5-µm packing L7

Flow rate: 1 mL/min

Injection volume:

 20 µL for 12-mg Tablets

100 µL for all other strengths

Run time: NLT 2 times the retention time of ropinirole

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at each time point (i):

Result = (rᵤ / rₛ) × C × V × (1 / L) × (M₁ / M₂) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

C = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

M₁ = molecular weight of ropinirole free base = 260.37

M₂ = molecular weight of ropinirole hydrochloride = 296.84

The percentages of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2. 

Test 2

Medium: Buffer 1; 500 mL.

Apparatus 2: 100 rpm

Times: 2, 12, and 24 h

Mobile phase: Acetonitrile, methanol, and Buffer 2 (14:6:80)

Standard solution: (L/400) mg/mL of USP Ropinirole Hydrochloride RS in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-µm pore size

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 12.5-cm; 5-µm packing L7

Flow rate: 1 mL/min

Injection volume:

20 µL for 12-mg Tablets

100 µL for all other strengths

Run time: NLT 2 times the retention time of ropinirole

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at each time point (i):

Result = (rᵤ / rₛ) × C × V × (1 / L) × (M₁ / M₂) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

C = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

M₁ = molecular weight of ropinirole free base = 260.37

M₂ = molecular weight of ropinirole hydrochloride = 296.84

Tolerances: See Table 2

The percentages of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

Test 3

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Buffer: 1.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.5.

Medium: 0.1 N hydrochloric acid VS; 500 mL

Apparatus 2: 100 rpm, with sinkers

Times: 1, 6, 12, and 24 h

Mobile phase: Acetonitrile and Buffer (10:90)

▲Standard stock solution:

0.23 mg/mL of USP Ropinirole Hydrochloride RS prepared as follows.

Transfer an appropriate amount of USP Ropinirole Hydrochloride RS to a suitable volumetric flask.

Add Mobile phase to about 50% of the final volume, and sonicate to dissolve.

Dilute with Mobile phase to volume.▲ (USP 1-May-2021)

Standard solution:

(L/500) mg/mL of USP Ropinirole Hydrochloride RS▲ from the Standard stock solution▲ in Medium, where L is the label claim in mg/Tablet

Sample solution:

Pass a portion of the solution under test through a suitable filter of 10-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L1

Column temperature: 35°C

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 2 times the retention time of ropinirole

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT ▲2.0▲ (USP 1-May-2021)

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (Cᵢ) of ropinirole (C₁₆H₂₄N₂O) in the sample withdrawn from the vessel at each time point (i):

Result = (rᵤ / rₛ) × C

rᵤ = peak response of ropinirole and 3-oxo ropinirole from the Sample solution

[Note—The relative retention times for ropinirole and 3-oxo ropinirole are 1.0 and ▲0.93▲, respectively]

rₛ = peak response of ropinirole from the Standard solution

C = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at each time point (i):

Result = C × V × (1 / L) × (M₁ / M₂) × 100

Result = {[C × (V − V₁)] + (C × V₁)} × (1 / L) × (M₁ / M₂) × 100

Result = ({C × [V − (2 × V₁)]} + [(C + C₁) × V₁]) × (1 / L) × (M₁ / M₂) × 100

Result = ({C × [V − (3 × V₁)]} + [(C + C₁ + C₂) × V₁]) × (1 / L) × (M₁ / M₂) × 100

C = concentration of ropinirole in the Sample solution at the specified time point (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

M₁ = molecular weight of ropinirole free base = 260.37

M₂ = molecular weight of ropinirole hydrochloride = 296.84

V₁ = volume of the Sample solution withdrawn at each time point (mL)

The percentages of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

Test 4

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Buffer: 1.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.5.

Medium: Buffer; 500 mL

Apparatus 2: 100 rpm, with sinkers

Times: 1, 6, 12, and 24 h

Mobile phase: Acetonitrile and Buffer (10:90)

Standard stock solution: 0.23 mg/mL of USP Ropinirole Hydrochloride RS prepared as described in Test 3

Standard solution: (L/500) mg/mL of USP Ropinirole Hydrochloride RS from the Standard stock solution in Medium, where L is the label claim in mg/Tablet

Sample solution:

Pass a portion of the solution under test through a suitable filter of 10-µm pore size

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L1

Column temperature: 35°C

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 2 times the retention time of ropinirole

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (Cᵢ) of ropinirole (C₁₆H₂₄N₂O) in the sample withdrawn from the vessel at each time point (i):

Result = (rᵤ / rₛ) × C

rᵤ = peak response of ropinirole and 3-oxo ropinirole from the Sample solution

[Note—The relative retention times for ropinirole and 3-oxo ropinirole are 1.0 and 0.93, respectively]

rₛ = peak response of ropinirole from the Standard solution

C = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at each time point (i):

Result = C × V × (1 / L) × (M₁ / M₂) × 100

Result = {[C × (V − V₁)] + (C × V₁)} × (1 / L) × (M₁ / M₂) × 100

Result = ({C × [V − (2 × V₁)]} + [(C + C₁) × V₁]) × (1 / L) × (M₁ / M₂) × 100

Result = ({C × [V − (3 × V₁)]} + [(C + C₁ + C₂) × V₁]) × (1 / L) × (M₁ / M₂) × 100

C = concentration of ropinirole in the Sample solution at the specified time point (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

M₁ = molecular weight of ropinirole free base = 260.37

M₂ = molecular weight of ropinirole hydrochloride = 296.84

V₁ = volume of the Sample solution withdrawn at each time point (mL)

The percentages of the labeled amount of ropinirole (C₁₆H₂₄N₂O) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.

IMPURITIES

Change to read:

• Organic Impurities

Solution A: 0.05% (v/v) triuoroacetic acid in water

Solution B: Acetonitrile and methanol (80:20)

Mobile phase: See Table 5.

Diluent 1: Acetonitrile and Solution A (80:20)

Diluent 2: Diluent 1 and Solution A (20:80)

System suitability solution: 0.03 mg/mL of USP Ropinirole Hydrochloride RS and 0.001 mg/mL of USP Ropinirole Related Compound B RS in

Diluent 2. Sonication may be used to aid dissolution.

Sensitivity solution: 0.015 µg/mL of USP Ropinirole Hydrochloride RS in Diluent 2

Standard solution: 0.15 µg/mL of USP Ropinirole Related Compound B RS in Diluent 2

Sample stock solution: Nominally 0.13–0.14 mg/mL of ropinirole from a suitable number of Tablets containing 20–50 mg of ropinirole

prepared as follows. Homogenize an appropriate number of Tablets in a suitable volume of Diluent 1. Pass a portion of the solution through

a nylon lter of 0.45-µm pore size and use the ltrate.

Sample solution: Nominally 26–28 µg/mL of ropinirole from the Sample stock solution and Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 100 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

Suitability requirements

Resolution: NLT 2.0 between ropinirole related compound B and ropinirole, System suitability solution

Relative standard deviation: NMT 10% for ropinirole related compound B, Standard solution

Signal-to-noise ratio: NLT 10 for ropinirole, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ropinirole related compound B in the portion of Tablets taken

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (Mᵣ₁/Mᵣ₂) × 100

rᵤ = peak response of ropinirole related compound B from the Sample solution

rₛ = peak response of ropinirole related compound B from the Standard solution

Cₛ = concentration of USP Ropinirole Related Compound B RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of ropinirole in the Sample solution (µg/mL)

Mᵣ₁ = molecular weight of ropinirole related compound B free base, 274.36

Mᵣ₂ = molecular weight of ropinirole related compound B hydrochloride, 310.82

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (rᵤ/F)/[Σ(rᵤ/F) + rᴿ] × 100

rᵤ = peak response of each degradation product from the Sample solution

F = relative response factor for the corresponding degradation product from Table 6

rᴿ = peak response of ropinirole from the Sample solution

Acceptance criteria: See Table 6. Disregard peaks less than 0.05%.

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

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

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

ᵈ ▲1,1'-Methylenebis{4-[2-(dipropylamino)ethyl]indolin-2-one}▲ (USP 1-May-2021).

ᵉ (Z)-4-[2-(Dipropylamino)ethyl]-3-propylideneindolin-2-one.

ᶠ Process impurity included in the table for identification only. Process impurities are controlled in the drug substance and are not to be reported or included in the total degradation products for the drug product.

5 ADDITIONAL REQUIREMENTS

Packaging & Storage: Preserve in well-closed containers, store at controlled room temperature.

Labeling: When more than one Dissolution test is given, label states test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Ropinirole Hydrochloride RS

USP Ropinirole Related Compound B RS

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

C₁₆H₂₂N₂O₂ · HCl 310.82