Oseltamivir Phosphate 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

Oseltamivir Phosphate Capsules contain Oseltamivir Phosphate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of oseltamivir (C₁₆H₂₈N₂O₄).

2 IDENTIFICATION

The retention time of the major peaks of the Sample solution corresponds to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

Oseltamivir

Solution A: Dissolve 6.8 g of potassium dihydrogen phosphate in 980 mL of water. Adjust with 1 M potassium hydroxide solution to a pH of 6.0, and dilute with water to 1 L.

Mobile phase: Methanol, acetonitrile, and Solution A (245:135:620)

Diluent: Methanol, acetonitrile, and 0.01 N phosphoric acid (245:135:620)

Standard solution: 1 mg/mL of USP Oseltamivir Phosphate RS in Diluent

Sample solution: Weigh the contents of 20 Capsules, and mix. Prepare the equivalent of about 1 mg of oseltamivir phosphate per mL, based on the label claim, by first dispersing a suitable portion of the powder in about 40% of the flask volume of Diluent using an ultrasonic bath for about 20 min, and diluting with Diluent to volume. Centrifuge an aliquot of this solution, and use the supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm × 25-cm; packing L7

Column temperature: 50°

Flow rate: 1.2 mL/min

Injection size: 15 μL

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 percentage of the labeled amount of oseltamivir (C₁₆H₂₈N₂O₄) 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 Oseltamivir Phosphate RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of oseltamivir, 312.41 (CN 1-Aug-2024)

M_r2 = molecular weight of oseltamivir phosphate, 410.40

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

4.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 20 mi

Detector: UV 240 nm

Standard solution: Prepare a solution in Medium having a known concentration of about 0.11 mg/mL of USP Oseltamivir Phosphate RS.

Quantitatively dilute a portion of this solution with Medium to obtain a solution having a known concentration similar to the expected concentration in the solution under test.

Sample solution: Pass a portion of the solution under test through a suitable filter of 1-μm pore size.

Excipients solution: Suspend an amount of the Placebo mixture equivalent to the weight of the excipients in one dosage unit and one empty Capsule shell in 900 mL of Medium. Heat to 37°, and filter.

Analysis

Samples: Medium, Standard solution, Sample solution, and Excipients solution

Determine the amount of oseltamivir phosphate (C₁₆H₂₈N₂O₄ · H₃PO₄) dissolved by measuring the absorbance at about 240 nm of the

Sample solution and Excipients solution in comparison with the Standard solution, using the Medium as the blank. Calculate the percentage of oseltamivir phosphate dissolved:

Result = [(A_U− A_E) × C_S × V × 100]/(A_S × L)

A_U = absorbance of the Sample solution

A_E = absorbance of the Excipients solution

C_S = concentration of USP Oseltamivir Phosphate RS in the Standard solution

V = volume of Medium, 900 mL

A_S = absorbance of the Standard solution

L = label claim for oseltamivir phosphate (mg/Capsule)

Tolerances: NLT 75% (Q) of the labeled amount of oseltamivir phosphate 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, deaerated

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with 8 N potassium hydroxide solution to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer (25:75)

Standard solution: (L/500) mg/mL of oseltamivir from USP Oseltamivir Phosphate RS in Medium, where L is the label claim in mg/Capsule. Sonicate to dissolve, if necessary.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size, discarding the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

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

Column temperature: 50°

Flow rate: 1.2 mL/min

Injection volume: 15 μL

Run time: NLT 1.5 times the retention time of oseltamivir

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 percentage of the labeled amount of oseltamivir (C₁₆H₂₈N₂O₄) dissolved:

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

r_U = peak response of oseltamivir from the Sample solution

r_S = peak response of oseltamivir from the Standard solution

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

V = volume of the Medium, 500 mL

M_r1 = molecular weight of oseltamivir, 312.41 (CN 1-Aug-2024)

M_r2 = molecular weight of oseltamivir phosphate, 410.40

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of oseltamivir (C₁₆H₂₈N₂O₄) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Solution A, Mobile phase, Diluent, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of individual impurities in the portion of Capsules taken:

Result = (r_U /r_S ) × (C_S /C_U) × (1/F) × (M_r1/M_r2) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response from the Standard solution

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

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

F = relative response factor from Table 1

M_r1 = molecular weight of oseltamivir, 312.41 (CN 1-Aug-2024)

M_r2 = molecular weight of oseltamivir phosphate, 410.40

Acceptance criteria: See Table 1.

Table 1

^a (3R,4R,5S)-4-Acetylamino-5-amino-3-(pentan-3-yloxy)-1-cyclohexene-1-carboxylic acid. (CN 1-Aug-2024)

^b Ethyl 4-acetylamino-3-hydroxy-benzoate. (CN 1-Aug-2024)

^c Ethyl (3R,4R,5S)-5-acetylamino-4-amino-3-(pentan-3-yloxy)-1-cyclohexene-1-carboxylate. (CN 1-Aug-2024)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

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

USP Reference Standards 〈11〉

USP Oseltamivir Phosphate RS