Aripiprazole Tablets

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

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

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1 DEFINITION

Aripiprazole Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂).

2 IDENTIFICATION

2.1 A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

Standard: Add 30 mL of ethyl acetate to 30 mg of USP Aripiprazole RS. Shake for 10 min, centrifuge for NLT 5 min, and pass the supernatant through a suitable membrane filter. To the filtrate add 15 mL of water, shake for 5 min, and centrifuge for NLT 10 min. Transfer 20 mL of the upper layer to a container and add anhydrous Magnesium sulfate, as needed. Shake well, pass through a suitable membrane filter, and evaporate the ethyl acetate on a water bath under reduced pressure. Use the residue. [NOTE-A centrifuge speed of 2000 rpm may be suitable.]

Sample: Grind a suitable number of Tablets and transfer a suitable portion of the ground Tablets, equivalent to 30 mg of aripiprazole, to an appropriate container. Add 30 mL of ethyl acetate, shake for 10 min, centrifuge for NLT 5 min, and pass the supernatant through a suitable membrane filter. To the filtrate add 15 mL of water, shake for 5 min, and centrifuge for NLT 10 min. Transfer 20 mL of the upper layer to a container and add a suitable amount of anhydrous magnesium sulfate. Shake well, pass through a suitable membrane filter, and evaporate the ethyl acetate on a water bath under reduced pressure. Use the residue. [NOTE-A centrifuge speed of 2000 rpm may be suitable.]

Analysis

Samples: Standard and Sample

Acceptance criteria: Meet the requirements

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

3 ASSAY

3.1 PROCEDURE

Solution A: 2.8 g/L of anhydrous sodium sulfate in water

Mobile phase: Acetonitrile, methanol, Solution A, and glacial acetic acid (33:11:56:1)

Internal standard solution: 0.33 mg/mL of USP Propylparaben RS in Mobile phase

Standard stock solution: 1 mg/mL of USP Aripiprazole RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Aripiprazole RS prepared as follows. Transfer 10.0 mL of Standard stock solution and 10.0 mL of Internal standard solution to a 50-mL volumetric flask, and dilute with Mobile phase to volume.

Sample solution: Nominally 0.2 mg/mL of aripiprazole from Tablets prepared as follows. Powder NLT 20 Tablets and transfer a suitable portion of the powder to an appropriate volumetric flask. Add 40% of the final flask volume of Mobile phase and 20% of the final flask volume of Internal standard solution. Shake for 10 min, and dilute with Mobile phase to volume. Centrifuge, if necessary, and pass the supernatant through a suitable filter of NMT 0.5-µm pore size, discard the first 1 mL of filtrate, and use the subsequent filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of aripiprazole

System suitability

Sample: Standard solution

[NOTE-The relative retention times for aripiprazole and propylparaben are about 1.0 and 1.5, respectively.]

Suitability requirements

Resolution: NLT 8 between aripiprazole and propylparaben

Tailing factor: NMT 1.7 for aripiprazole and for propylparaben

Relative standard deviation: NMT 2.0% for the peak response ratio of aripiprazole to propylparaben

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) in the portion of Tablets taken:

Result = (R_U/R_S) x (C_S/C_U) × 100

R_U= peak response ratio of aripiprazole to propylparaben from the Sample solution

R_S = peak response ratio of aripiprazole to propylparaben from the Standard solution

C_S = concentration of USP Aripiprazole RS in the Standard solution (mg/mL)

C_U = nominal concentration of aripiprazole in the Sample solution (mg/mL)

Acceptance criteria: 95.0%-105.0%

4 PERFORMANCE TESTS

Change to read:

4.1 DISSOLUTION (711)

Test 1

Medium: pH 1.2 hydrochloric acid buffer (Transfer 250 mL of 14.9 g/L of potassium chloride in water to a 1-L volumetric flask, add 425 mL of 0.2 N hydrochloric acid, and dilute with water to volume. Degas the resulting solution or pass the resulting solution through a filter under vacuum.), degassed; 900 mL

Apparatus 2: 60 rpm

Time: 30 min

Procedure: Determine the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) dissolved by using either the Spectrometric

procedure or the Chromatographic procedure described below.

Spectrometric procedure

Standard stock solution: 1 mg/mL of USP Aripiprazole RS in alcohol

Standard solution: (L/900) mg/mL of USP Aripiprazole RS from 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, discarding the first 5 mL of filtrate.

Instrumental conditions

Mode: UV

Analytical wavelengths: 249 and 325 nm

Cell length: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) dissolved:

Result = (A_U/A_S) × C × V × (1/L) × 100

A_U = absorbance at 249 nm minus the absorbance at 325 nm of the Sample solution

A_S = absorbance at 249 nm minus the absorbance at 325 nm of the Standard solution

C_S = concentration of USP Aripiprazole RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Chromatographic procedure

Solution A: 2.8 g/L of anhydrous sodium sulfate

Solution B: 13.9 g/L of glacial acetic acid and 23.9 g/L of sodium acetate in water

Mobile phase: Acetonitrile, methanol, Solution A, and glacial acetic acid (40:10:50:1)

Diluent: Solution B and methanol (50:50)

Internal standard solution: 0.67 µg/mL of USP Propylparaben RS in Diluent

Standard stock solution A: 1 mg/mL of USP Aripiprazole RS in Mobile phase

Standard stock solution B: 0.002 mg/mL of USP Aripiprazole RS from Standard stock solution A in Medium passed through a suitable filter of NMT 0.5-µm pore size, discarding the first 6 mL of filtrate

Standard solution: 0.001 mg/mL of USP Aripiprazole RS from Standard stock solution B prepared by combining 5 mL of Standard stock solution B and 5 mL of Internal standard solution

Sample stock solution: Pass a portion of the solution under test through a suitable filter of NMT 0.5-µm pore size, discarding NLT the first 6 mL of filtrate.

Sample solution: Combine 2 mL of Sample stock solution with 2 mL of Internal standard solution.

Chromatographic system: Proceed as directed in the Assay except as follows.

Injection volume: 100 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for aripiprazole and propylparaben are about 1.0 and 1.8, respectively.]

Suitability requirements

Resolution: NLT 10 between aripiprazole and propylparaben

Relative standard deviation: NMT 1.5% for the peak response ratio of aripiprazole to propylparaben

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) dissolved:

Result = (R_U/R_S) × C_S × V × ^▲D ×_▲(ERR 1-Sep-2023) (1/L) × 100

R_U = peak response ratio of aripiprazole to propylparaben from the Sample solution

R_S = peak response ratio of aripiprazole to propylparaben from the Standard solution

C_S = concentration of USP Aripiprazole RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

^▲D = dilution factor of the Sample solution, _▲(ERR 1-Sep-2023)

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid VS; 900 mL

Apparatus 2: 60 rpm

Time: 15 min

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with 1 N phosphoric acid TS to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard stock solution: 0.11 mg/mL of USP Aripiprazole RS in solution prepared as follows. Transfer a suitable amount of USP

Aripiprazole RS to an appropriate volumetric flask. Add 2% of the flask volume of acetonitrile and 70% of the flask volume of Medium.

Sonication may be used to promote dissolution. Dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Aripiprazole RS from 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, discarding NLT the first 5 mL of filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 5-µm packing L7

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 5 µL

Run time: NLT 1.6 times the retention time of aripiprazole

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L) x 100

r_U = peak response of aripiprazole from the Sample solution

r_S = peak response of aripiprazole from the Standard solution S

C_S = concentration of USP Aripiprazole RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) is dissolved.

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

Medium: 5.82 g/L of dibasic sodium phosphate and 16.7 g/L of citric acid monohydrate in water

For Tablets labeled to contain 2 and 5 mg: 500 mL

For Tablets labeled to contain 10, 15, 20, and 30 mg: 900 mL

Apparatus 1

For Tablets labeled to contain 2 and 5 mg: 50 rpm

For Tablets labeled to contain 10, 15, 20, and 30 mg: 100 rpm

Times

For Tablets labeled to contain 2 and 5 mg: 15 min

For Tablets labeled to contain 10, 15, 20, and 30 mg: 30 min

Mobile phase: Acetonitrile and water (40:60). Add 2 mL of triethylamine to each liter of the mixture. Adjust with phosporic acid to a pH of 3.0.

Diluent: Acetonitrile and water (40:60). Add 2 mL of triethylamine to each liter of the mixture. Adjust with phosphoric acid to a pH of 2.5.

Standard stock solution A: 0.4 mg/mL of USP Aripiprazole RS in Diluent. Sonicate to dissolve, if necessary.

Standard stock solution B: 0.28 mg/mL of USP Aripiprazole RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution A (for Tablets labeled to contain 2 and 5 mg): (L/500) mg/mL of USP Aripiprazole RS from Standard stock solution A in Medium, where L is the label claim in mg/Tablet

Standard solution B (for Tablets labeled to contain 10, 15, 20, and 30 mg): (L/900) mg/mL of USP Aripiprazole RS from Standard

stock solution B 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 0.45-µm pore size, discarding the first 5 mL of the

filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 217 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of aripiprazole

System suitability

Sample: Standard solution A or B

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution A or B and Sample solution

Calculate the percentage of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L) x 100

r_U = peak response of aripiprazole from the Sample solution

r_S = peak response of aripiprazole from Standard solution A or Standard solution B

C_S = concentration of USP Aripiprazole RS in Standard solution A or Standard solution B (mg/mL)

V = volume of corresponding Medium, 500 or 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of aripiprazole (C23H27CI2N₃O₂) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Protect solutions from light.

Buffer: 9.6 g/L of dibasic ammonium citrate, 1.6 g/L of citric acid, and 2.9 g/L of sodium dodecyl sulfate in water. Adjust with 11 g/L of dibasic ammonium citrate in water or 9.6 g/L of anhydrous citric acid in water to a pH of 4.7, if needed.

Mobile phase: Acetonitrile and Buffer (45:55)

Diluent: Acetonitrile, water, and glacial acetic acid (40:60:1)

System suitability solution: 0.5 mg/mL of USP Aripiprazole RS, and 0.0005 mg/mL each of USP Aripiprazole Related Compound F RS and USP Aripiprazole Related Compound G RS in Diluent

Sample solution: Nominally 0.5 mg/mL of aripiprazole from Tablets prepared as follows. Powder NLT 20 Tablets, transfer a suitable portion of the powder equivalent to NLT 4 mg of aripiprazole to an appropriate container, and add a suitable volume of Diluent. Shake for 10 min and centrifuge, if necessary. Pass the supernatant through a suitable filter of NMT 0.5-µm pore size, discard the first 1 mL of filtrate, and use the subsequent filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of aripiprazole

System suitability

Sample: System suitability solution [NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 3 between aripiprazole related compound G and aripiprazole

Signal-to-noise ratio: NLT 10 for aripiprazole related compound F and aripiprazole related compound G

Analysis

Sample: Sample solution

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

Result = (r_U/r_T) x 100

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

r_T = sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1. Disregard peaks that are less than 0.1% of the aripiprazole peak.

Table 1

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at controlled room temperature.

6.2 LABELING

The labeling states the Dissolution test used only if Test 1 is not used.

6.3 USP REFERENCE STANDARDS (11)

USP Aripiprazole RS

USP Aripiprazole Related Compound FRS

4-(2,3-Dichlorophenyl)-1-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy) butyl] Piperazine 1-oxide.

C₂₃H₂₇CI₂N₃O₃  464.38

USP Aripiprazole Related Compound G RS

7-(4-[4-(2,3-Dichlorophenyl) piperazin-1-yl]butoxy)quinolin-2(1H)-one.

C2₃H₂₅CI₂N₃O₂  446.37

USP Propylparaben RS