Aripiprazole Orally Disintegrating 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 Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of aripiprazole (C₂₃H₂₇CI₂N₃O₂).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A (CN 1-MAY-2020)

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

3.1 PROCEDURE

Solution A: 2.84 g/L of sodium sulfate in water

Buffer: 3.48 g/L of dibasic potassium phosphate adjusted with phosphoric acid to a pH of 8.2

Mobile phase: Acetonitrile and Buffer (50:50)

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

Diluent B: Acetonitrile and 0.1 M hydrochloric acid (20:80)

System suitability solution: 0.01 mg/mL each of USP Aripiprazole RS and USP Aripiprazole Related Compound G RS in Diluent A. Sonication and shaking may be used to aid in dissolution.

Standard solution: 0.25 mg/mL of USP Aripiprazole RS in Diluent B. Sonication may be used to aid in dissolution.

Sample solution: Nominally 0.2-0.3 mg/mL of aripiprazole from NLT 5 Orally Disintegrating Tablets prepared as follows. Transfer NLT 5 Orally Disintegrating Tablets to a suitable volumetric flask and dilute with Diluent B to NMT 75% of the final flask volume. Sonicate for 5 min and shake for 15 min. Dilute with Diluent B to volume. Pass the resulting solution through a suitable filter and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 252 nm

Column: 4.6-mm × 10-cm; 3.5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 1.4 times the retention time of aripiprazole

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times of aripiprazole related compound G and aripiprazole are 0.74 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between aripiprazole related compound G and aripiprazole, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response 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: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISINTEGRATION (701)

NMT 60 s

4.2 DISSOLUTION (711)

Medium: pH 4.0 sodium acetate trihydrate buffer (3.0 g/L of sodium acetate prepared as follows. Transfer a suitable quantity of sodium acetate to a suitable container containing 90% of the final container volume of water. Adjust with glacial acetic acid to a pH of 4.0. Add water to the final volume.), degassed; 1000 mL

Apparatus 2: 75 rpm

Time: 30 min

Mobile phase: Acetonitrile and 0.025 M hydrochloric acid (40:60)

Standard solution: (L/1000) mg/mL of USP Aripiprazole RS in Mobile phase 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 few mL.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 225 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 times the retention time of aripiprazole

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

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) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

V = volume of Medium, 1000 mL

L = label claim (mg/Tablet)

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

4.3 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A: Water and trifluoroacetic acid (100:0.05)

Solution B: Acetonitrile and trifluoroacetic acid (100:0.05)

Solution C: 2.84 g/L of sodium sulfate in water

Mobile phase: See Table 1.

Table 1

[NOTE-The gradient was established on an HPLC system with a dwell volume of approximately 1.0 mL.]

Diluent: Acetonitrile, methanol, Solution C, and glacial acetic acid (33:11:56:1)

System suitability solution: 250 µg/mL of USP Aripiprazole RS, and 0.5 µg/mL each of USP Aripiprazole Related Compound F RS and USP Aripiprazole Related Compound G RS in Diluent. Sonication may be used to aid in dissolution.

Sample solution: Nominally 0.2-0.3 mg/mL of aripiprazole from NLT 5 Orally Disintegrating Tablets prepared as follows. Transfer NLT 5 Orally Disintegrating Tablets to a suitable volumetric flask. Add about 70% of the total volume of Diluent. Sonicate for 10 min and shake for 10 min. Dilute with Diluent to volume. Pass the resulting solution through a suitable filter and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: System suitability solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 4.0 between aripiprazole related compound G and aripiprazole; NLT 1.5 between aripiprazole and aripiprazole related

compound F

Analysis

Sample: Sample solution

Calculate the total peak response for individual impurities and aripiprazole from the Sample solution:

Result = Σ[r_i x (1/F)] + r_U

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

F = relative response factor (see Table 2)

r_U = peak response of aripiprazole from the Sample solution

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

Result = (r_i/r_T) x (1/F) x 100

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

r_T = total peak response for individual impurities and aripiprazole from the Sample solution

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at controlled room temperature.

6.2 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