Duloxetine Delayed-Release 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

Duloxetine Delayed-Release Capsules contain an amount of Duloxetine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of duloxetine (C₁₈H₁₉NOS).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPE Пентинкалки Тасть (197), Infrared Spectroscopy: 197F.

Buffer: 6.9 g/L of monobasic sodium phosphate in water adjusted with 5 N sodium hydroxide to a pH of 7.5

Spectral range: 1650 cm^-1 to 900 cm^-1

Standard: 1 mg/mL of USP Dulcesine Hydrachloride RS in methylene chloride Shake the contents, and sonicate for 1 min. Transfer 15 mL of Filtrate into a separatory funnel, and add 15 mL of Buffer. Collect the organic layer, and evaporate to dryness. Redissolve the residue with a few drops of methylene chloride, and transfer to a potassium bromide or sodium chloride plate. Allow it to dry.

Sample: 1 mg/mL of duloxetine, from the contents of NLT 10 Capsules in methaitone chloride. Proceed as directed in the Standard

Acceptance criteria: Meet the requirements

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

Change to read:

PROCEDURE

Protect solutions of duloxetine from light.

Buffer A: 3.4 g/L of monobasic notassium phosphate in water. Τo 1 L of this solution add 15 ml of grietthidamine, and adjust with phosphoric acid to a pH of 5.5.

Buffer B: 0.2 g/L of monobasic ammonium phosphate and 4.5 g/L of dibasic entassium phosphate in water. Adjust with phosphonic acid to a pH of 8.0.

Mobile phase: Methanol, tetrahydrofuran, and Buffer A 

Diluent: Methanol and Buffer 8 (50:50)

System suitability solution: 0.1 mg/mL of ISP Quloxetine Hydrochloride RS, 0.05 mg/ml. of e-naphthol, 0.01 mg/ml. of ISP Duloxetine Related Compound FRS, and 0.025 mg/ml. of USP Duloxetine Related Compound HRS in Diluent (Nore-Add 1 ml of methanol before diluting to volume to assist with dissolving contents. Duloxetine related compound His used for peak identification purposes in this solution]

Standard solution: 0.1 mg/ml of USP Duloxetine Hydrochloride RS in Diluent

Sample solution: Nominally 0.1 mg/mL of duloxetine from the contents of NLT 5 Capsules, in Diluent

Chromatographie system

(See Chromatography (621), System Suitability)

Note-It is recommended to preheat the Mobile phase to 45°.]

Mode: LC

Detector: UV 230 mm

Column: 4.6-mm × 7.5-cm; 3- or 3.5-μm packing L7

Column temperature: 45°

Flow rate: 1.5 mL/min

Injection volume: 10 µl

Run time: 6 times the retention time of duloxetine

System suitability

Samples: System suitability solution and Standard solution

Nom See Table 2 in Organic Impurities for relative retention times.]

Suitability requirements

Resolution: NLT 1 fi between duloxetine and duloxetine related compound F. NLT 2 between a-naphthol and duloxetine related compound

H. System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of duloxetine (C, H, NOS) in the portion of Capsules taken:

Result = (r_U/(r_S) × (C_S /C_U) x (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 Duloxetine Hydrochlonde RS in the Standard solution (mg/ml)

C_U = nominal concentration of duloxetine in the Sample solution (mg/ml)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Acceptance criteria: 90.0%-110.0%

PERFORMANCE TESTS

Change to read

Dissolution (711)

Test 1

Acid stage

Acid stage medium: 0.1 N hydrochloric acid VS: 1000 ml

Apparatus 1: 100 гр/т

Time: 2 h

Buffer stage

Buffer stage medium: pH 6.8 phosphate buffer: 1000 mL

Apparatus 1: 100 rpm

Time: 60 min for Capsules containing 20% w/w pellets, 90 min for Capsules containing 32% w/w pellets

Buffer A and Mobile phase: Proceed as directed in the Assay

Standard stock solution: 0.28 mg/ml of USP Duloxetine Hydrochionde RS equivalent to 0.25 mg/ml, of duloxetine, in Buffer stage medium

Use a small amount of methanol, not exceeding 2% of the final volume, to dissolve duloxetine

Acid stage standard solutise: 0.0023 mg/ml of USP Dulcoxetine Hydrochloride R, equivalent to 0.002 mg/ml of duloxetine, from the Standard stock solution diluted with Buffer stage medium

Buffer stage standard solution: 0.023 mg/ml of USP Duloxetine Hydrochloride RS, equivalent to 0.02 mg/ml, of duloxetine, from the

Standard stock solution diluted with Buffer stage medium

Sample solution: After 2 h in the Acid stage medium, pass a portion of the solution under test through a suitable filter. Transfer the basket containing the pellets to the vessel containing the fluffer stage medium. After the appropriate time in the Buffer stage medium, pass a portion of the solution under test through a suitable fiter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6mm x 7.5cm; 3- or 3.5µm packing L7

Column temperature: 45°

Flow rate: 1.5 ml/min

Injection volume: 10 μL.

System suitability

Sample: Acid stage standard solution

[No-The relative retention times for duloxetine and a-naphthol are 1.0 and 1.4, respectively]

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Acid stage standard solution, Buffer stage standard solution, and Sample solztion

Calculate the concentration of duloxetine in the Acid stage medium (C)

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

r_U = peak response of duloxetine from the Sample solution

r_S = peak response of duloxetine from the Acid stage standard solution

C_S = concentration of USP Duluxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the equivalent concentration of duloxetine from a-naphthol in the Acid stage medium (C)

Result = (r_U/(r_S) × C_S x (M_r1/M_r2) x (M_r1/M_r3)

r_U = peak response of a-naphthol from the Sample solution

r_S = peak response of duloxetine from the Acid stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/ml)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

M_r3 = molecular weight of a-naphthol, 144.17

Calculate the percentage of the labeled amount of duloxetine dissolved in the Acid stage medium (0)

Result = (C₁ + C₂) x V x (1/L) x 100

C₁ = concentration of duloxetine in the Acid stage medium (mg/mL)

C₂ = equivalent concentration of duloxetine from a-naphthol in the Acid stage medium (mg/mL)

V = volume of Medium, 1000 ml

L = label claim of duloxetine (mg/Capsule)

Calculate the percentage of the labeled amount of duloxetine dissolved in the Buffer stage medium

Result = [(r_U/(r_S) × (C_S/L) x V x (M_r1/M_r2) x 100] + Q_A

r_U = peak response of duloxetine from the Sample solution

r_S = peak response of duloxetine from the Buffer stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium, 1000 mL

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

M_r3 = molecular weight of a-naphthol, 144.17

Q_A = percentage of the labeled amount of duloxetine dissolved in the Acid stage medium

Tolerances

Acid stage: No individual unit releases more than 10% of the labeled amount of duloxetine in 2 h.

Buffer stage

For Capsules containing 20% w/w pellets: NLT 75% (Q) of the labeled amount of duloxetine is dissolved in 60 min.

For Capsules labeled to contain 32% w/w pellets: NLT 75% (4) of the labeled amount of duloxetine is dissolved in 90 min.

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

Protect solutions of duloxetine from light

Acid stage

Acid stage medium: 0.1 N hydrochloric acid VS: 750 ml

Apparatus 2: 100 грm.

Time: 2 h in Acid stage medium

Buffer stage

Buffer stage medium of 6.8 phosphate buffer (after 2 h, add 250 ml of 76 g/L of tribasic sodium phosphate, previously heated to 37 t

0.5°, to the Acid stage medium), 1000 ml.

Apparatus 2: 100 rpm

Time: 3 h in Buffer stage medium. The time in Buffer stage medium includes the time in Acid stage medium.

Solution A: A mixture of tristhylamine and water prepared as follows. Add 15 ml. of triethylamine to 1 L of water and adjust with phosphong aold to a pH of 2.5±0.05.

Mobile phase: Acetonitrile and Solution A (40:60)

Diluent: 0.1 N hydrochloric acid VS and 76 g/L of tribasic sodium phosphate (75:25)

Standard stock solution: 0.46 mg/ml of USP Duloxetine Hydrochloride RS, equivalent to 0.4 mg/ml of duloxetine, prepared as follows Transfer a suitable amount of USP Duloxetine Hydrachloride RS to an appropriate volumetric flask and dissolve in 50% of the final flask

volume of Mobile phase. Dilute with Mobile phase to volume.

Standard solution: 0.048 mg/ml of USP Dulovatine Hydrochloride RS, equivalent to 0.04 mg/ml. of duloxetine, from the Standard stock

solution in Diluent

Acid stage sample solution and Buffer stage sample solution: Pass a portion of the solution under test through a suitable filter, and use.

the filtrate. Note-A cannula-style filter with a 20-um pore size may be suitable]

Chromatographic system

(See Chromatography (621). Svotem Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6mm x 15.0-cm 3-um packing LI

Column temperature: 40

Flow rate: 1.3 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution, Acid stage sample solution, and Buffer stage sample solution

Calculiste the percentage of the labeled amount of duloxetine (C₁₈H₁₉NOS) dissolved in Acid stage medium

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

r_U = peak response of duloxetine from the Acid stage sample solution

r_S = peak response of duloxetine from the Standard solution

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

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

V = volume of Acid stage medium, 750 ml.

L = label claim of duloxetine (mg/Capsule)

Calculate the percentage of the labeled amount of duloxetine (CHNOS) dissolved in Buffer stage medium

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

r_U = peak response of duloxetine from the Buffer stage sample solution

r_S = peak response of duloxetine from the Standard solution

C_S = concentration of US Duloxetine Hydrochloride RS in the Standard solution (mg/ml)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

V = volume of Buffer stage medium, 1000 ml

L = label claim of duloxetine (mg/Capsule)

Tolerances

Acid stage: For each individual value, NMT 10% of the labeled amount of duloxetine (C₁₈H₁₉NOS). The percentage of the labeled amount of duloxetine dissolved at the time specified conforms to Dissolution (711). Accectance Table 3

Buffer stage: NLT BO0% (Q) of the labeled amount of duloxetine (C₁₈H₁₉NOS). The percentage of the labeled amount of duloxetine dissolved at the time specified conforms to Dissolution (711), Acceptance Table 4

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

Protect solutions of duloxetine from light

Acid stage

Acid stage medium: 0.1 N hydrochloric acid VS with pegal (mix 8.5 ml of bydrochloric acid and 3.2 g of gegain in 1 L of water): 1000 ml

Apparatus 1: 100 грm

Time: 2 h in Acid stage medium

Buffer stage

Buffer stage medium: gr 6.8 phosphate buffer (6.8 g/L of monobasic potassium phosphate and 0.9 g/L of sodium hydroxide in water adjusted with ghosphoric acid or 1 N sodium hydroxide VS to a pit of 6.80); 1000 mL

Apparatus 1: 100 гpm

Time: 3 h in Buffer stage medium. The time in Buffer stage medium includes the time in Acid stage medium..

Procedure: Aftor 2 h in the Acid stage medium, withdraw a sample from the solution and immediately filter. Remove and rinse each basket with NMT 25 mL of 0.1 N hydrochloric acid YS (ERR 2010) Then transfer the baskets to the Buffer stage medium.

Solution A: 2.7 g/L of monobasic potassium phosphate in water. Add 2.0 ml of truthvanine per liter of solution and adjust with abosphoric acid to a pH of 6.0.

Mobile phase: Acetonitrile and Solution A (28:62)

Standard stock solution: 1.1 mg/mL of USP Duloxetine Hydrochloride RS, equivalent to 1.0 mg/mL of duloxetine, prepared as follows.

Transfer a suitable amount of USP Duloxetine Hydrochloride RS to an appropriate volumetric flask and dissolve in 60% of the flask volume of water. Sonication may be used to promote dissolution. Dilute with water to volume.

System suitability stock solution: 0.011 mg/ml of USP Duloxetine Hydrochloride RS from the Standard stock solution in 2.1. Nhydrochloric acid VS. Store this solution in a 37" water bath for 30 min.

System suitability solution: 0.002 mg/mL of USP Duloxetine Hydrochloride RS from the System sultability stock solution in Mobile phase

Pass the resulting solution through a suitable filter and use the filtrate,

Acid stage standard stock solution: 0.11 mg/mL of USP Duloxetine Hydrochloride RS, equivalent to 0.10 mg/ml of duloxetine, from the Standard stock solution in water

Acid stage standard solution: (1/50,000) mg/ml. of duloxetine from the Standent stock solution in Mobile phase, where L is the label claim, in mg/Capsule

Buffer stage standard solution: (1/1,000) mg/ml of duloxetine from the Standard stock solution in Buffer stage medium, where is the label claim, in mg/Capsule

Acid stage sample solution: Transfer 2 mL of the solution under test to a suitable container and dilute with Mobile phase to 10 ml. Pass a portion of the resulting solution through a suitable filter, discard NLT 3 ml, and use the filtrate

Buffer stage sample solution: Pass a portion of the solution under test through a suitable fliter, discard NLT 1 mL, and use the filtrate.

Chromatographic system

(See Chromatography (671) System Suitability)

Mode: LC

Detector: UV 230 nm

Column: 4.6mm x 15.0-cm 3.5-um packing L

Column temperature: 50°

Flow rate: 1.1 mL/min

Injection volume: 10 μL.

Run time: NLT 2 times the retention time of duloxetine

System suitability

Samples: System suitability solution and Buffer stage standard solution

[Nom The relative retention times for duloxetine and a-naphthol are 1.0 and 1.7, respectively)

Suitability requirements

Resolution: NLT 5 between duloxetine and a-naphthol, Systern suitability solution

Tailing factor: NMT 2.0, Buffer stage standard solution

Relative standard deviation: NMT 2.0%, Buffer stage standard solution

Analysis

Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the concentration of duloxetine (C₁₈H₁₉NOS) dissolved in the Acid stage medium (C₁):

Result = (r_U/(r_S) × C_S x D x (M_r1/M_r2)

r_U = peak response of duloxetine from the Acid stage sample solution

r_S = peak response of duloxetine from the Acid stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/ml)

D = dilution factor of the Acid stage sample solution

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the equivalent concentration of duloxetine from naphthol in the Acid stage medium (C₂)

Result = (r_U/(r_S) × C_S x D x (1/F) x (M_r1/M_r2)

r_U = peak response of α-naphtholfrom the Acid stage sampie solution

r_S = k response of duloxetine from the Acid stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/ml)l)

D = dilution factor of the Acid stage sample solution

F = relative response factor of α-naphthol, 1.7

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the equivalent concentration of duloxetine from all of the unspecified degradation products in the Acid stage medlum (C₃):

Result = (r_U/(r_S) × C_S x D x (M_r1/M_r2)

r_U = sum of the peak responses from all of the unspecified degradation products in the Acid stage sample solution

r_S = pesk response of duloxetine from the Acid stage: standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)

D = dilution factor of the Acid stage sample solution

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the percentage of the labeled amount of duloxetine dissolved in the Acid stage medium:

Result = (ΣC_i) x V x (1/L) x 100

C_i = concentration or equivalent concentration of duloxetine in the Aold stage medium (mg/mL)

V = volume of Acid stage medium, 1000 ml.

L = label claim of duloxetine (mg/Capsule)

Calculate the percentage of the labeled amount of duloxetine dissolved in both the Acid stage medium and the Buffer stage medium:

Result = [(r_U/(r_S) × C_S x (M_r1/M_r2) x V x (1/L) x 100] + Q_A

r_U = peak response of duloxetine from the Buffer stage sample solution

r_S = peak response of duloxetine from the Buffer stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

V = volume of Buffer stage medium, 1000 mL

L = label claim (mg/Capsule)

Q_A = percentage of the labeled amount of duloxetine dissolved in the Acid stage medium

Tolerances

Acid stage: For each individual value, NMT 10% of the labeled amount of duloxetine (C₁₈H₁₉NOS). The percentage of the labeled amount of duloxetine dissolved at the time specified conforms to Dissolution 17111. Accectance Table 3

Buffer stage: NLT 75% (Q) of the labeled amount of duloxetine (C₁₈H₁₉NOS). The percentage of the labeled amount of duloxetine dissolved at the time specified conforms to Dissolution (711). Accentance Table 4

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

Protect solutions of duloxetine from light.

Acid stage

Acid stage medium: 0.1. N hydrochloric acid VS, 1000 ml

Apparatus 1: 100 rpm

Time: 2 h in Acid stage medium

Buffer stage

Buffer stage medium pit.6.8.phosphate buffer (6.8 g/t of monobasic potassium phosphate and 0.9 g/t of sodium hydroxide in water

adjusted with ghosphoric acid or 1. N sodium hydroxide VS 10 a pH of 6.80); 1000 ml

Apparatus 1:100 грm

Time: 3 h in Buffer stage medium. The time in Buffer stage medium includes the time in Acid stage mediam.

Procedure: After 2 h in the Acid stage medium, withdraw a sample from the solution under test and immediately filter. Remove the Acid

stage medium and add the Buffer stage medium

Solution A: Acetonitrile and water (20:80). To each liter add 1.0 ml. of phosphoric acid

Solution B: Acetonitrile

Mobile phase: See Table 1.

Acid stage standard stock solution: 0.011 mg/ml, of LISP Duloxetine Hydrochloride RS, equivalent to 0.010 mg/ml, of duloxetine, in methanol. Use this solution within 10 h

Acid stage standard solution: (L/20,000) mg/mL of dulcoxetine from the Standerd stock solution in solution prepared as follows, where i is the label claim, in mg/Capsulevolume of Acid stage standard stock solution to an appropriate volumetric flask. Add 45% of the flask volume of 0.1 N hydrochloric acid VS and dilute with 01 N sodium hydroxide Vii to volume. Use this solution within 10 h.

Buffer stage standard stock solution: 0.67 mg/ml of USP Diloxetine Hydrochloride RS, equivalent to 0.6 mg/ml. of duloxetine, in acetomtrile

Buffer stage standard solution: (L/1,000) mg/mL of duloxetine from Buffer stage standard stock solution in Buffer stage medium

Acid stage sample stock solution: Pass a of the solution under test through a suitable filter, discard NLT 1 ml, and use the filtrate.

Use this solution within 4 h.

Acid stage sample solution: Dilute 5.0 mL of the Acid stage sample stock solution with 2.1. N sodium hydroxide VS to 10 mil. Use this solution within 4h

Buffer stage sample solution: Pass a portion of the solution under test through a suitable filter, discard NLT 2 mL, and use the filtrate.

Further dilute with Buffer stage medium, if needed.

Chromatographic system

(See Chromatography (621) System Suitability)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 10.0-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Sample: Acid stage standard solution

No-The relative retention times for duloxetine 4-naphthyl isomer, duloxetine, and e-naphthol are 0.8, 1.0, and 1.5, respectively

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.01

Instrumental conditions

(See Ultraviolet Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 291 nm

Blank: Buffer stage medium

System suitability

Sample: Buffer stage standard solution

Suitability requirements

Relative standard deviation: NMT 2.03

Analysis

Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the concentration of duloxetine (C₁₈H₁₉NOS) dissolved in the Acid stage medium (C₁):

Result = (r_U/(r_S) × C_S x D x (M_r1/M_r2)

r_U = peak response of duloxetine from the Acid stage sample solution

r_S = peak response of duloxetine from the Acid stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)

D = dilution factor of the Acid stage sample solution, 2

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the equivalent concentration of duloxetine from a naphthol in the Acid stage medium (C₂):

Result = (r_U/(r_S) × C_S x D x (1/F) x (M_r1/M_r2)

r_U = peak response of e-naphthol from the Acid stage sample solution

r_S = peak response of duluxetine from the Acid stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Acid stage standard solution (mg/ml)

D = dilution factor of the Acid stage sample solution, 2

F = relative response factor of α-naphthol, 1.7

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the equivalent concentration of dufexetine from duloxetine 4-naphthyl isomer (4-13-(Methylamino)-1-(thiophen-2-yl)propyl naphthalen-1-ol) in the Acid stage medium (C3):

Result = (r_U/(r_S) × C_S x D x (1/F) x (M_r1/M_r2)

r_U = peak response of duloxetine 4-naphthyl isomer from the Acid stage sample solution

r_S = peak response of duloxetine from the Acid stage standard solution

C_S = equivalent concentration of duloxetine from enaphthol in the Acid stage medium (mg/ml)

D = dilution factor of the Acid stage sample solution, 2

F = relative response factor of duloxetine 4-naphthyl isomer, 0.70

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

Calculate the percentage of the labeled amount of duloxetine dissolved in Acid stage medium (Q_A)

Result = (ΣC_i) x V x (1/L) x 100

C_i = concentration or equivalent concentration of duloxetine in the Aold stage medium (mg/ml) associated with duloxetine, a naphthol, and duloxetine 4-naphthyl isomer

V = volume of Acid stage medium, 1000 ml.

L = label claim of duloxetine (mg/Capsule)

Calculate the percentage of the labeled amount of duloxetine dissolved in the Buffer stage medam

Result = (A_U/A_S) [C_S x (M_r1/M_r2)] x V x D x (1/L)×100

A_U = absorbance of duloxetine from the Buffer stage sample solution

A_S = absorbance of duloxetine from the Buffer stage standard solution

C_S = concentration of USP Duloxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)

M_r1 = molecular weight of duloxetine free base, 297.42

M_r2 = molecular weight of duloxetine hydrochloride, 333.88

V = volume of Buffer stage medium, 1000ml

D = dilution factor of the Buffer stage sample solution, if needed

L = label claim (mg/Capsule)

Tolerances

Acid stage: NMT TO% of the labeled amount of duloxetine (C₁₈H₁₉NOS). The percentage of the labeled amount of duloxetine dissolved at

the time specified conforme to Dissolution (711) Acceptance Table 3.

Buffer stage: NLT 75% (2) of the labeled amount of duloxetine (C, H, NOS). The percentage of the labeled amount of duloxetine dissolved at the time specified conforms to resolution (711), Accectance Table 4

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

4 IMPURITIES

Change to read:

Protect solutions of duloxetine from light

ffer B, Moblie phase, Diluent, System suitability solution, Standard solution, Sample solution, Chromatographic system, and Buffer A, Buffer

System suitability: Proceed as directed in the Assay

Analysis

Sample: Sample solution

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

Result = (r_U/(r_S) × 100

r_U = peak response for each impurity

r_S = sum of all the peak responses

Acceptance criteria: See Table 2

^a This is a process impurity that is included for identification purposes orily. It is controlled in the drug substance and is not to be reported or included in total impurities

^b Naphthalen-1-ol

^c May not be present in all formulations.

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature

LABELING: The labeling states with which Dissolution test the article complies, if other than Test 1.