Orlistat 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

Orlistat Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of orlistat (C₂₉H₅₃NO₅).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

3 ASSAY

Change to read:

3.1 Procedure

Mobile phase: Acetonitrile, phosphoric acid, and water (860: 0.05: 140)

Standard solution: 0.6 mg/mL of USP Orlistat RS in Mobile phase

Sample solution: Nominally 0.6 mg/mL of orlistat in Mobile phase prepared as follows. Transfer a quantity of orlistat from the contents of Capsules (NLT 10) to a suitable volumetric flask. Add 70% of the final volume of Mobile phase and sonicate for 1 min. Shake the resulting solution mechanically for 15 min and dilute with Mobile phase to volume. Pass a portion of this solution through a filter of 0.45-μm or finer pore size, discarding the first few milliliters of filtrate.

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 195 nm

Column: 3.9-mm × 15-cm; 4-μm packing L1

Flow rate: 1.0 mL/min

Injection volume: 20 μL

Run time: NLT 5.5 times the retention time of orlistat (IRA 1-Jan-2022)

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of orlistat (C₂₉H₅₃NO₅) in the portion of Capsules taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of orlistat from the Sample solution

r_S = peak response of orlistat from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 3% sodium lauryl sulfate and 0.5% sodium chloride in water. To each 10 L of media, add 1–2 drops of n-octanol, and adjust with phosphoric acid to a pH of 6.0; 900 mL

Apparatus 2: 75 rpm, with coil wire sinker

Time: 45 min

Mobile phase: Acetonitrile and water (86:14)

Standard solution: 0.13 mg/mL of USP Orlistat RS prepared as follows. Transfer a quantity of USP Orlistat RS to a suitable volumetric flask.

Dissolve in 2% of the final volume of acetonitrile, and dilute with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.2-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode, Detector, and Column: Proceed as directed in the Assay.

Flow rate: 2.0 mL/min

Injection volume: 50 μL

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 orlistat (C₂₉H₅₃NO₅) dissolved:

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

r_U = peak response of orlistat from the Sample solution

r_S = peak response of orlistat from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 900 mL

Tolerances: NLT 75% (Q) of the labeled amount of orlistat (C H NO ) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Mobile phase, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.6 mg/mL of USP Orlistat RS and 0.5 μg/mL of orlistat related compound D prepared by dissolving a suitable amount of USP Orlistat RS and diluting USP Orlistat Related Compound D Solution RS in Mobile phase (IRA 1-Jan-2022)

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 1.4 between orlistat and orlistat related compound D, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

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

r_S = peak response of orlistat from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a(2S,3R,5S)-5-[(Formyl-l-leucyl)oxy]-2-hexyl-3-hydroxyhexadecanoic acid.

^b(2S,3S,5S)-5-[(Formyl-l-leucyl)oxy]-2-hexyl-3-hydroxyhexadecanoic acid.

^c (S)-3-Hexyl-6-undecyl-5,6-dihydro-2H-pyran-2-one.

^d(S,E)-Henicos-7-en-10-yl formyl-l-leucinate.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at 25°, excursions permitted between 15° and 30°.

Change to read:

USP Reference Standards 〈11〉

USP Orlistat RS

USP Orlistat Related Compound D Solution RS

Orlistat related compound D;

(3S,4R,6S)-3-Hexyl-2-oxo-6-undecyltetrahydro-2H-pyran-4-yl formyl-l-leucinate.

C₂₉H₅₃NO₅ 495.75 (IRA 1-Jan-2022)