Sodium alendronate Tablets

Alendronic Acid Tablets,

Sodium Alendronate Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of, C₄H₁₃NO₇P₂.

Usual strengths. 5 mg; 10 mg; 35 mg; 70 mg.

Identification

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

Mobile phase. A mixture of 1 volume of 13.5 M ammonia, 8 volumes of 2.5 per cent v/v solution of trichloroacetic acid and 11 volumes of methanol.

Test solution. Weigh a quantity of the powdered tablet containing 76 mg of sodium alendronate, disperse in 50.0 ml of water for 30 minutes with the aid of ultrasound and occasional shaking, and filter.

Reference solution. A 0.2 per cent w/v of sodium alendronate RS.in water.

Apply to the plate 2 µl of each solution. Allow the mobile phase to raise 15 cm. After development, dry the plate in hot air 100 ± 5^o. The principal spot in the chromatogram obtained with the test solution corresponds in position and colour to the spot in the chromatogram obtained with reference solution.

1. In the Assay, the principal peak in the chromatogram obtained with test solution corresponds to that in the chromatogram obtained with reference solution.

Tests

Dissolution (2.5.2).  

Apparatus No. 1,

Medium. 900 ml of  water,

Speed and time. 50 rpm and  45 minutes.

Withdraw a suitable volume of the medium and filter.

Determine by liquid chromatography (2.4.14).

Test solution.  Dilute the filtrate with  water, to produce a solution containing 0.00084 per cent w/v of sodium alendronate.

Reference solution. A  0.0011 per cent w/v solution of sodium alendronate RS in water.

Chromatographic system

      –  a stainless steel column 15 cm x 4.6 mm, packed with anion exchange resin (7 µm) (Such as Allsep Anion),

–  column temperature. 35°,

–  mobile phase: a 0.02 per cent v/v solution of formic acid, pH adjusted to 3.5 with sodium hydroxide,

     –   flow rate: 1.2 ml per minute,

     –   refractive index detector, maintained at 40°,

     –   injection volume: 100 µl.

Inject the reference solution and the test solution.

Calculate the content of C₄H₁₃NO₇P₂ in the tablet.

2. Not less than 75 per cent of the stated amount ofC₄H₁₃NO₇P₂.

Phosphate and phosphite. Determine by liquid chromatography (2.4.14).

Test solution. Shake a quantity of the powdered tablets containing 0.1 g of sodium alendronate, add 20 ml of water and mix with the aid of ultrasound for 30 minutes. Add sufficient water to produce 25.0 ml and filter.

Reference solution. A 0.0024 per cent w/v solution of orthophosphoric acid and 0.002 per cent w/v solution of phosphorous acid in water.

Use the chromatographic system as described under Dissolution. Allow the chromatography to proceed for twice the retention time of the principal peak.

Inject reference solution. The relative retention times with reference to alendronic acid (retention time, about 17 minutes) are: phosphate, about 1.3; phosphite, about 1.6.

Inject the reference solution. The test is not valid unless the signal to noise ratios of the peaks due to phosphate and phosphite are not less then10.

Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of each peak due to phosphate and phosphite is not more than the area of the principal peak in the chromatogram obtained with reference solution   (0.5 per cent).

 4-Aminobutanoic acid. Determine by liquid chromatography (2.4.14).

Buffer solution. A solution containing 0.294 per cent w/v of sodium citrate and 0.142per cent w/v of anhydrous disodium hydrogen orthophosphate, adjust to pH 8.0 using orthophosphoric acid and filter.

Test solution. Shake a quantity of the powdered tablets containing 23.0 mg of sodium alendronate with a 2.94 per cent w/v solution of sodium citrate, to produce 50.0 ml, mix and filter; discard the first 5 ml of filtrate. To 5 ml of the filtrate in a screw cap centrifuge tube add 5 ml of a 1.91per cent w/v solution of sodium borate, 10 mL of a 0.2per cent w/v solution of (9-fluorenyl)methyl chloroformate in acetonitrile, shake for 1 minute and allow to stand at room temperature for 30 minutes, add 20 ml of dichloromethane and shake vigorously for 1 minute; centrifuge and use the aqueous layer.

Reference solution (a). Dilute 5.0 ml solution containing 0.003 per cent w/v solution of 4-aminobutanoic acid in a 2.94 per cent w/v solution of sodium citrate in a screw cap centrifuge tube add 5 ml of a 1.91 per cent w/v solution of sodium borate, 10 ml of a 0.2 per cent w/v solution of (9-fluorenyl)methyl chloroformate in acetonitrile, shake for 45 seconds and allow to stand at room temperature for 30 minutes, add 20 ml of dichloromethane and shake vigorously for 1 minute, centrifuge and use the aqueous layer.

Reference solution (b). Dilute 5.0 ml solution containing 0.06 per cent w/v of sodium alendronate RS and 0.01 per cent w/v of 4-aminobutanoic acid in a 2.94 per cent w/v solution of sodium citrate in a screw cap centrifuge tube add 5 ml of a 1.91 per cent w/v solution of sodium borate, 10 ml of a 0.2 per cent w/v solution of (9-fluorenyl)methyl chloroformate in acetonitrile, shake for 45 seconds and allow to stand at room temperature for 30 minutes, add 20 ml of dichloromethane and shake vigorously for 1 minute; centrifuge and use the aqueous layer.

Chromatographic system

      –  a stainless steel column 25 cm x 4.1 mm, packed with styrene-divinylbenzene co-polymer (10 µm) (Such as Hamilton PRP-1),

– column temperature. 45°,

–   mobile phase A. a mixture of 15 volumes of acetonitrile and 85 volumes of buffer solution;

1.   B. a mixture of 70 volumes of acetonitrile and 30 volumes of buffer solution,

      –  flow rate: 1.8 ml per minute,

     –   spectrophotometer set at 266 nm,

      –  injection volume: 20 µl.

              Time           Mobile phase A          Mobile phase B

           (in min.)          (per cent v/v)               (per cent v/v)

                  0                         100                                  0

                15                        100                                  0

                25                         50                                  50

                27                          0                                  100

                32                        100                                  0

                40                        100                                  0

                  

Inject reference solution (b). The test is not valid unless the resolution between the peaks due to sodium alendronate and aminobutanoic acid, is not less than 10.0.                                                                                                                                                                                                                                                                                                                        

Inject reference solution (a) and the test solution. In the chromatogram obtained with the test solution, the area of peak due to 4-aminobutanoic acid is not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent).

Other tests. Comply with the tests stated under Tablets.

Assay. Determine by liquid chromatography (2.4.14).

Test solution. Weigh and powder 20 tablets. Disperse a quantity of the powder containing 50 mg of Sodium Alendronate with 20 ml of water for 30 minutes with the aid of ultrasound and occasional shaking, and agitate until cool, add sufficient to produce 25.0 ml, mix and filter

Reference solution. A 0.2 per cent w/v solution of sodium alendronate RS in the water.

Use chromatographic system as described under Dissolution.

Inject the reference solution and the test solution.

Calculate the content of C₄H₁₃NO₇P₂ in the tablets.

1 mg of C₄H₁₂NNaO₇P₂,3H₂O is equivalent to 0.7662 mg of C₄H₁₃NO₇P₂.

Labelling. The label states the strength in terms of the equivalent amount of sodium alendronate.