Modafinil Tablets
Modafinil Tablets contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of modafinil, C15H15NO2S.
Usual strengths. 100 mg: 200 mg.
Identification
Extract a quantity of powdered tablets containing 0.1 g of modafinil with 50 ml each of dichlormethane 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. On the residue determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with modafinil RS treated in the same manner or with the reference spectrum of modafinil.
Tests
Dissolution (2.5.2).
Apparatus No. 1,
Medium. 900 ml of 0.1 M hydrochloric acid,
Speed and time. 50 rpm for 30 minutes.
Withdraw a suitable volume of the medium and filter. Reject the first few ml of the filtrate and dilute a suitable volume of the filtrate with dissolution medium. Measure the absorbance of the resulting solution at the maximum at about 222 nm (2.4.7). Calculate the content of modafinil, C15H15NO2S. in the medium from the absorbance obtained from a solution of known concentration of modafinil RS in the dissolution medium.
- Not less than 75 per cent of the stated amount of C15H15NO2S.
Related substances. Determine by liquid chromatography (2.4.14), as described under assay with the following modifications.
Name Relative Correction
retention time factor
Modafinil 1.0 ---
Salicylic acid impurity A1 1.1 ---
Modafinil acid impurity B2 1.4 1.0
Modafinil sulphone impurity C3 1.7 1.1
1 salicylic acid is used for calculating resolution and is not apotential impurity,
2 2-[(diphenylmethyl)sulphenyl]acetic acid,
3 2-[(diphenylmethyl)sulphonyl]acetamide,
Inject reference solution (a). The test is not valid unless the resolution between the peaks due to modafinil and salicylic acid is not less than 1.3 and the relative standard deviation of replicate injections is not more than 2.0 per cent for the modafinil peak.
Inject the test solution. . The area of the peak due to modafinil acid impurity and modafinil sulphone impurity is not more than 0.5 per cent each, the area of any other secondary peak is not more than 0.2 per cent and the sum of areas of all the secondary peaks is not more than 1.5 per cent, calculated by area normalisation.
Other tests. Comply with the tests stated under Tablets.
Assay. Determine by liquid chromatography (2.4.14).
Solvent mixture A. A mixture of 35 volumes of acetonitrile and 65 volumes of water.
Solvent mixture B. A mixture of 35 volumes of acetonitrile, 65 volumes of water and 1 volume of acetic acid.
Test solution. Weigh and powder 20 tablets. Weigh and transfer a quantity of the powder containing 100 mg of Modafinil to a 250.0 ml volumetric flask, add 200 ml of solvent mixture B and disperse with the aid of ultrasound for about 5 minutes with intermittent shaking. Dilute with solvent mixture B to volume, mix and filter, rejecting the first few ml of filtrate.
Reference solution (a). A 0.0005 per cent w/v solution of modafinil RS and 0.001 per cent w/v solution of salicylic acid RS in the solvent mixture A.
Reference solution (b). A 0.04 per cent w/v solution of modafinil RS in the solvent mixture B.
Charomatographic system
– a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),
– column temperature: 40°,
– mobile phase: a mixture of 35 volumes of acetonitrile and 65 volumes of a buffer solution prepared by dissolving 6.8 g of potassium dihydrogen phosphate in 900 ml of water, adjusted the pH to 2.3 with orthophosphoric acid and diluting to
1000 ml with water,
– flow rate: 1 ml per minute,
– spectrophotometer set at 220 nm,
– injection volume: 5 µl.
The relative retention times of modafinil and salicylic acid are about 1.0 and 1.1 respectively.
Inject reference solution (a). The test is not valid unless the resolution between the peaks due to modafinil and salicylic acid is not less than 1.3, the tailing factor for modafinil peak is not more than 1.5 and the relative standard deviation of replicate injections is not more than 2.0 per cent for the modafinil peak.
Inject the test solution and reference solution (b).
Calculate the content of C15H15NO2S in the tablets.
Storage. Store protected from light and moisture, at a temperature below 30°.