Fluoxetine Capsules

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

Fluoxetine Capsules contain an amount of Fluoxetine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Nominally 10 mg of fluoxetine from Capsules prepared as follows. Transfer a portion of Capsule contents, equivalent to 10 mg of fluoxetine, to a suitable container. Dissolve in 10 mL of methanol and pass through a suitable filter. Rinse the container and filter with 5 mL of methanol, and evaporate with the aid of a current of air and mild heat to dryness.

Acceptance criteria: Meet the requirements

3 ASSAY

3.1 Procedure

Buffer: Triethylamine and water (1:98), adjusted with phosphoric acid to a pH of 6.0

Mobile phase: Stabilizer-free tetrahydrofuran, methanol, and Buffer (30:10:60)

Standard solution: 0.11 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sample solution: Nominally 0.1 mg/mL of fluoxetine from Capsules prepared as follows. Remove, as completely as possible, the contents of NLT 20 Capsules and mix. Transfer a suitable portion of the contents to an appropriate volumetric flask and dissolve in Mobile phase. Dilute with Mobile phase to volume. Pass the resulting solution through a suitable filter, and use the filtrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 227 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Fluoxetine Hydrochloride RS in the Standard solution (μg/mL)

C_U = nominal concentration of fluoxetine in the Sample solution (μg/mL)

M_r1 = molecular weight of fluoxetine, 309.33

M_r2 = molecular weight of fluoxetine hydrochloride, 345.79

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Solution A: Transfer 250 mL of acetonitrile to a suitable container, add 1.0 mL of diethylamine, mix, and adjust with phosphoric acid to a pH of 3.5. [Note-Diethylamine phosphate will precipitate; therefore, keep it well-mixed.]

Mobile phase: Acetonitrile, diethylamine, and water (400:4:600), adjusted with phosphoric acid to a pH of 3.5

Standard stock solution: USP Fluoxetine Hydrochloride RS having a concentration similar to that of the Sample stock solution passed through a suitable filter. Use the filtrate.

Standard solution: Transfer 5.0 mL of Standard stock solution to a suitable container, add 2.0 mL of Solution A, and mix.

Sample stock solution: Pass 20 mL of the solution under test through a suitable filter. Use the filtrate.

Sample solution: Transfer 5.0 mL of Sample stock solution to a suitable container, add 2.0 mL of Solution A, and mix.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 15-cm; packing L10

Flow rate: 2 mL/min

Injection volume: 50 μL

4.1.2 System suitability

Sample: Standard solution

4.1.3 Suitability requirements

Relative standard deviation: NMT 2.0%

4.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) dissolved:

Result = (r_U /r_S ) × C_S × (M_r1/M_r2) × V × (1/L) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

M_r1= molecular weight of fluoxetine, 309.33

M_r2 = molecular weight of fluoxetine hydrochloride, 345.79

V = volume of Medium, 900 mL

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) is dissolved.

4.2 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; 500 mL

Apparatus 2: 50 rpm, with sinkers

Time: 30 min

Solution A: Transfer 250 mL of acetonitrile to a suitable container, add 1.0 mL of diethylamine, mix, and adjust with phosphoric acid to a pH of 3.5. [Note—Diethylamine phosphate will precipitate; therefore, keep it well-mixed.]

Mobile phase: Acetonitrile and water (40:60). Add 4 mL of diethylamine to each liter of the solution. Adjust with phosphoric acid to a pH of 3.5.

Standard stock solution: 0.027 mg/mL of USP Fluoxetine Hydrochloride RS prepared as follows. Transfer 27 mg of USP Fluoxetine Hydrochloride RS to a 50-mL volumetric flask, add 30 mL of Mobile phase, and sonicate for NLT 5 min. Cool and dilute with methanol to volume. Transfer 5 mL of the solution to a 100-mL volumetric flask and dilute with Medium to volume. Pass the solution through a suitable filter of 0.45-μm pore size, discard NLT 3 mL, and use the filtrate.

Standard solution: Transfer 5.0 mL of Standard stock solution to a suitable container, add 2.0 mL of Solution A, and mix.

Sample stock solution: Withdraw and pass 10 mL of the solution under test through a suitable filter, discarding NLT 3 mL. Dilute the filtrate with Medium to a concentration similar to that of the Standard stock solution, if necessary.

Sample solution: Transfer 5.0 mL of Sample stock solution to a suitable container, add 2.0 mL of Solution A, and mix.

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 25-cm; 5-μm packing L10

Flow rate: 2 mL/min

Injection volume: 50 μL

Run time: NLT 2 times the retention time of fluoxetine

4.2.2 System suitability

Sample: Standard solution

4.2.3 Suitability requirements

Relative standard deviation: NMT 2.0%

4.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) dissolved:

Result = (r_U /r_S ) × C_S × (M_r1/M_r2) × V × D × (1/L) × 100

r_U = peak response of fluoxetine from the Sample solution

r_S = peak response of fluoxetine from the Standard solution

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

M_r1 = molecular weight of fluoxetine, 309.33

M_r2 = molecular weight of fluoxetine hydrochloride, 345.79

V = volume of Medium, 500 mL

D = dilution factor for the Sample stock solution

L = label claim (mg/Capsule)

Tolerances: NLT 80% (Q) of the labeled amount of fluoxetine (C₁₇H₁₈F₃NO) is dissolved. (RB 1-Mar-2023)

Uniformity of Dosage Units 〈905〉: Meet the requirements

IMPURITIES

Organic Impurities

Buffer: Triethylamine and water (1:98), adjusted with phosphoric acid to a pH of 6.0

Mobile phase: Acetonitrile and Buffer (35:65)

System suitability solution: 0.01 mg/mL of USP Fluoxetine Hydrochloride RS in Mobile phase

Sample solution: Nominally 2 mg/mL of fluoxetine from Capsules prepared as follows. Remove, as completely as possible, the contents of NLT 20 Capsules and mix. Transfer a suitable portion of the contents to an appropriate volumetric flask and dissolve in Mobile phase. Dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L10

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 22 min

System suitability

Sample: System suitability solution

Suitability requirements

Column efficiency: NLT 1100 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Capsules taken:

Result = (r_i/r_T) × 100

r_i = peak response of each impurity from the Sample solution

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

Acceptance criteria

Any individual impurity: NMT 0.25%

Total impurities: NMT 0.80%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Add the following:

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. (RB 1-Mar-2023)

USP Reference Standards 〈11〉

USP Fluoxetine Hydrochloride RS