Modafinil 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

Modafinil Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of modafinil (C₁₅H₁₅NO₂S).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A _{(USP 1-May-2021)}

Standard: _{(USP 1-May-2021)} Transfer a quantity, in milligrams, of USP Modafinil RS, equivalent to the labeled amount of modafinil, to a suitable container. Add 50 mL each of dichloromethane and water. Shake the mixture, and allow the layers to separate. Filter a portion of the lower (dichloromethane) layer, and evaporate to dryness, using a stream of nitrogen if necessary _{(USP 1-May-2021)}

Sample: _{(USP 1-May-2021)} Grind 1 Tablet, and add 50 mL each of dichloromethane and water. Shake the mixture, and allow the layers to separate. Filter a portion of the lower (dichloromethane) layer, and evaporate to dryness, using a stream of nitrogen if necessary. _{(USP 1-May-2021)}

Acceptance criteria: Meet the requirements

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-May-2021)}

3 ASSAY

Change to read:

PROCEDURE

Buffer: 6.8 g/L of potassium dihydrogen phosphate in water. Adjust with phosphoric acid to a pH of 2.3.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent A: Acetonitrile and water (35:65)

Diluent B: Acetonitrile, water, and acetic acid (35:65:1)

System suitability solution: 5 µg/mL of USP Modafinil RS and 10 µg/mL of USP Salicylic Acid RS in Diluent A

Standard solution: 0.4 mg/mL of USP Modafinil RS in Diluent B

Sample solution: 0.4 mg/mL of modafinil prepared as follows. _{(USP 1-May-2021)} Weigh and finely powder Tablets (NLT 20). Transfer a portion of the powder, equivalent to 100 mg of modafinil, to a 250-mL volumetric flask, add 200 mL of Diluent B, and sonicate for about 5 min with intermittent manual shaking. Dilute with Diluent B to volume, and mix. Passa portion _{(USP 1-May-2021)} through a suitable filter of 0.45-µm or finer pore size, and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 5 µL

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for modafinil and salicylic acid are about 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 1.3 between modafinil and salicylic acid

Tailing factor: NMT 1.5 for the modafinil peak

Relative standard deviation: NMT 2.0% for the modafinil peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of modanil (C₁₅H₁₅NO₂S) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of modanil from the Sample solution

r_s = peak response of modanil from the Standard solution

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

C_u = nominal concentration of modanil in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Test 1

Medium: 0.1 N hydrochloric acid: 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: Prepare a solution having a known concentration of USP Modafinil RS in Medium.

Sample solution: A filtered portion of the solution under test, suitably diluted with Medium if necessary Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: Absorption maximum at about 222 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage _{(USP 1-May-2021)} of modafinil (C₁₅H₁₅NO₂S) dissolved:

Result = (A_u /A_s ) × C_s × V × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet) _{(USP 1-May-2021)}

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

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: (L/900) mg/mL of USP Modanil RS, where L is the label claim in mg/Tablet. Prepare by dissolving the standard in a volume of methanol equivalent to 5%–10% of the nal volume and then diluting with Medium to volume.

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: Absorption maximum at about 225 nm

Cell: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of modanil (C₁₅H₁₅NO₂S) dissolved:

Result = (A_u /A_s ) × C_s × V × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of modanil (C₁₅H₁₅NO₂S) is dissolved.

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

Medium: 0.1 N hydrochloric acid; 900 mL, deaerated

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: (L/900) mg/mL of USP Modanil RS, where L is the label claim in mg/Tablet. Prepare by dissolving the standard in a volume of methanol equivalent to 5%–10% of the nal volume and then diluting with Medium to volume.

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

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: Absorption maximum at about 220 nm

Cell: 0.1 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of modanil (C₁₅H₁₅NO₂S) dissolved:

Result = (A_u /A_s ) × C_s × V × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of modanil (C₁₅H₁₅NO₂S) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Buffer, Mobile phase, Diluent B. _{(USP 1-May-2021)} System suitability solution, Sample solution, and Chromatographic system: Proceed as

directed in the Assay.

Sensitivity solution: 0.4 µg/mL of USP Modafinil RS in Diluent BA _{(USP 1-May-2021)}

System suitability

Samples: System suitability solution and Sensitivity solution _{(USP 1-May-2021)}

Suitability requirements

Resolution: NLT 1.3 between modafinil and salicylic acid, System suitability solution _{(USP 1-May-2021)}

Relative standard deviation: NMT 2.0% for the modafinil peak, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution _{(USP 1-May-2021)}

Analysis

Sample: Sample solution

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

Result = (r_U /r_T ) × (1/F) × 100

r_U = peak response of each individual impurity

r_T = sum of the responses of all the peaks

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.1%. _{(USP 1-May-2021)}

Table 1

^a Salicylic acid is used for calculating resolution and is not a potential impurity.

^b 2-[(Diphenylmethyl)sulnyl]acetic acid.

^c 2-[(Diphenylmethyl)sulfonyl]acetamide.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight 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 Modafinil RS

USP Salicylic Acid RS