Cilostazol 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

Cilostazol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂).

2 IDENTIFICATION

Delete the following:

. A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 1975

Standard solution: 100 mg/mL of USP Cilostazol RS in chloroform

Sample solution: Transfer the equivalent of 100 mg of cilostazol from finely powdered Tablets into a glass container. Add 1 mL of chloroform, shake for 1 min, and pass through a suitable filter of 0.5-µm or finer pore size. (USP 1-May-2021)

Add the following:

A. The UV spectrum of the major peak for cilostazol of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2021)

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

3 ASSAY

Change to read:

3.1 PROCEDURE

Mobile phase: Acetonitrile, methanol, and water (35:15:50)

Standard solution: 0.1 mg/mL of USP Cilostazol RS in Mobile phase prepared as follows. Transfer a quantity of USP Cilostazol RS to a suitable volumetric flask. Add Mobile phase to 80% of the total volume and sonicate for at least 15 min. Dilute with Mobile phase to volume, and mix well.

Sample stock solution: Transfer 10 Tablets to a 500-mL volumetric flask. Add Mobile phase to 80% of the total volume and shake mechanically for 30 min. Sonicate for at least 5 min. Dilute with Mobile phase to volume, and mix well.

Sample solution: Nominally 0.1 mg/mL of cilostazol in Mobile phase from the Sample stock solution. Pass through a suitable nylon filter of 0.45-µm pore size. Discard the first few milliliters of the filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing 11

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 2 times the retention time of the cilostazol peak

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of cilostazol from the Sample solution

r_S = peak response of cilostazol from the Standard solution

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

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

(USP 1-May-2021)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Test 1

Medium: 0.30% sodium lauryl sulfate in water, 900 mL

Apparatus 2: 75 rpm

Time: 60 min

Standard stock solution: 0.28 mg/ml. of USP Cilostazol RS in methanol (USP 1-May-2021)

Standard solution: 5.6 µg/mL of USP Cilostazol RS in Medium from the Standard stock solution (USP 1-May-2021)

Sample solution: Nominally 5.6 µg/mL of cilostazol in Medium prepared as follows. Pass NLT 20 mL of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 10 mL.. Dilute with Medium (USP 1-May-2021)

Instrumental conditions

Mode: UV

Analytical wavelength: 257 nm

Cell: 1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of (USP 1-May-2021) Cilostazol (C₂₀H₂₇N₅O₂) (USP 1-May-2021) dissolved:

Result = (A_U/A_s) x C_s x Vx D (USP 1-May-2021) × (1/L) x 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution (USP 1-May-2021)

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) (USP 1-May-2021) is dissolved.

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

Medium: 0.3% sodium lauryl sulfate in water, 900 mL, deaerated

Apparatus 2: 75 rpm

Time: 30 min

Standard stock solution: 1.1 mg/mL of USP Cilostazol RS in methanol (USP 1-May-2021)

Standard solution:(L/900) mg/mL of USP Cilostazol RS in 0.5% sodium lauryl sulfate in water from the Standard stock solution, where L is the label claim in mg/Tablet (USP 1-May-2021)

Sample solution: Pass a portion of the solution under test through a suitable filter.

Instrumental conditions

Mode: UV

Analytical wavelength: 258 nm

Cell: 0.2 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) dissolved:

Result = (A_U/A_s) x C_s x V x (1/L) x 100

A_U = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Cilostazol RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

(USP 1-May-2021)

Tolerances: NLT 75% (Q) of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) (USP 1-May-2021) is dissolved.

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

Medium: 0.3% sodium lauryl sulfate in water: 900 mL

Apparatus 2: 75 rpm

Time: 60 min

Standard stock solution, (USP 1-May-2021) Standard solution, Sample solution, and Instrumental conditions: Proceed as directed for

Test 1.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) dissolved:

Result = (A_U/A_s) x C_sxVxDx (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_s = concentration of USP Cilostazol RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution

L = label claim (mg/Tablet)

(USP 1-May-2021)

Tolerances: NLT 70% (Q) of the labeled amount of cilostazol (C₂₀H₂₇N₅O₂) (USP 1-May-2021) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Add the following:

ORGANIC IMPURITIES

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

System suitability solution: 0.1 mg/mL of USP Cilostazol RS and 1 µg/mL of USP Cilostazol Related Compound B RS in Mobile phase

Sensitivity solution: 0.05 µg/mL of USP Cilostazol RS in Mobile phase from the Standard solution

System suitability

Samples: Standard solution, System suitability solution, and Sensitivity solution

[NOTE-The relative retention times for cilostazol related compound A, cilostazol related compound B, and cilostazol are 0.25, 0.81, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between cilostazol related compound B and cilostazol, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) x (C_S/C_U) × 100

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

r_S = peak response of cilostazol from the Standard solution

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

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

Acceptance criteria

Any individual degradation product: NMT 0.2%

Total degradation products: NMT 0.3% (USP 1-May-2021)

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight and light-resistant containers. Store at controlled room temperature.

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

Change to read:

USP REFERENCE STANDARDS (11)

USP Cilostazol RS

USP Cilostazol Related Compound B RS

6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy)-1H-quinolin-2-one.

C₂₀H₂₅NO₂ 367.45 (USP 1-May-2021)