Nimodipine Tablets 

Nimodipine Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of nimodipine, C21H26N₂O7. They may be coated.

Usual strength. 30 mg.

NOTE: Carry out the following procedures protected from light or under long-wavelength light (greater than 420 nm). Prepare  the solutions immediately before use and protect them from light.

Identification

2. Determine by thin layer chromatography (2.4.17), coating the plate withsilica gel.

Mobile phase. A mixture of 40 volumes of ethyl acetate and 60 volumes of cyclohexane.

Test solution. Weigh a quantity of the powdered tablet containing 60 mg of nimodipine with 10 ml of ethyl acetate for 15 minutes, centrifuge and use the supernatant liquid.

Reference solution (a). A 0.6 per cent w/v solution of nimodipine RS in ethyl acetate.

Reference solution (b). A mixture of equal volumes of test solution and the reference solution.

Apply to the plate 2 µl of each solution. Allow the mobile phase to raise 15 cm. Dry the plate in air and examine under the ultraviolet light at 254 nm. Spray the plate with a freshly prepared 0.1 per cent w/v solution of 2,6-dichloroquinonechlorimide in ethanol and heat at 110° for about 3 minutes. The principal spot in the chromatogram obtained with the test solution correspond in position and colour to that in the chromatogram obtained with reference solution (a). The principal spot in the chromatogram obtained with reference solution (b) appears as a single, compact spot.

1. In the Assay, the principal peak in the chromatogram obtained with test solution corresponds to the peak in thechromatogram obtained with reference solution (a). 

Tests

Dissolution (2.5.2).

Apparatus No. 1,

Medium. 900 ml of acetate buffer pH 4.5 prepared by dissolving 3.0 g of sodium acetate in 50 ml of water, add 1.75 g of glacial acetic acid and dilute to 1000.0 ml with water, containing 0.3 per cent w/v solution of sodium dodecyl sulphate.

Speed and time. 75 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 340 nm (2.4.7). Calculate the content of nimodipine, C21H26N₂O7. in the medium from the absorbance obtained from a solution of known concentration of nimodipine RS in the dissolution medium.

7. Not less than 80 per cent of the stated amount of C21H26N₂O7.

Related substances. Determine by liquid chromatography (2.4.14).

Test solution. Disperse a quantity of the powdered tablets containing 60 mg of nimodipine with 50 of methanol with the aid of ultrasound for 5 minutes and dilute to 100.0 ml with methanol. Centrifuge and use the supernatant liquid.

Reference solution (a). Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase and further dilute 2.0 ml of this resulting solution to 10.0 ml with the mobile phase.

Reference solution (b). A 0.0003 per cent w/v solution of nimodipine impurity A RS [(2-methoxyethyl 1-methylethyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate] in the mobile phase.

Reference solution (c). A 0.0002 per cent w/v solution of nimodipine RS and nimodipine impurity A RS in the mobile phase.

Chromatographic system

     –   a stainless steel column 25 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),

     –   mobile phase:            a mixture of 13 volumes of acetonitrile, 26 volumes of tetrahydrofuran and 60 volumes of water.

     –   column temperature. 40°,

     –   flow rate: 1.5 ml per minute.

     –   spectrophotometer set at 235 nm,

     –   injection volume: 20 µl. 

Inject reference solution (c). The test is not valid unless the resolution between the peaks due to nimodipine and nimodipine impurity A is not less than 1.5 and the tailing factor of the peak due to nimodipine is not more than 2.0.

Inject reference solutions (a), (b) and the test solution. In the chromatogram obtained with the test solution, the area of any peak corresponding to nimodipine impurity A  is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) 
(0.5 per cent). The area of any other secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent). The sum of areas of all the secondary peaks other than nimodipine impurity A is not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) 
(0.5 per cent). Ignore any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).  

Other tests. Comply with the tests stated under Tablets.

Assay. Determine by liquid chromatography (2.4.14), as described under the related substances using following modifications.

Test solution. Weigh and powder 20 tablets.  Disperse a quantity of the powder containing 60 mg of Nimodipine with 50 ml of methanol, mix with the aid of ultrasound for 5 minutes and dilute to 100.0 ml with methanol. Centrifuge and use the supernatant liquid.

Reference solution (a). A 0.06 per cent w/v solution of nimodipine RS in methanol.

Reference solution (b). A 0.002 per cent w/v solution each of nimodipine RS and nimodipine impurity A RS in the methanol.

Inject reference solution (b). The test is not valid unless the resolution between nimodipine and nimodipine impurity A is not less than 1.5 and the tailing factor for nimodipine peak is not more than 2.0.

Inject reference solution (a) and the test solution .

Calculate the content of C₂₁H₂₆N₂O₇  in the Tablets.

Storage. Store protected from light, at a temperature below 30˚.