Pentoxifylline Prolonged-release Tablets

Pentoxifylline Extended-release Tablets; Pentoxifylline Sustained-release Tablets.

PentoxifyllineExtended-Release Tablets manufactured by different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable, as the dissolution profile of the products of different manufacturers may not be the same.

Pentoxifylline Extended- Release Tablets contain not less than 95.0 per cent and not more than 105.0 per cent of the stated amount of pentoxifylline, C13H18N₄O3.

Usual strengths. 100 mg; 400 mg.

Identification

A. Weigh and powder five tablets (a coarse screen may be used to separate the powder from the tablet film-coating if necessary). Weigh a quantity of powdered tablets containing 200 mg of pentoxifylline to a 15 ml centrifuge tube, add about 10 ml of methanol, cap the tube, and shake vigorously for about 5 minutes. Centrifuge for about 5 minutes to allow undissolved material to settle. Decant the supernatant into a suitable beaker, and evaporate the solution with the aid of a current of air to dryness at about 35˚. Dissolve the residue in about 15 ml of methylene chloride, transfer to a separatory funnel, add about 10 ml of water and shake. Allow the layers to separate, transfer the methylene chloride layer, and pass through anhydrous sodium sulphate, collecting the filtrate in a small beaker. Evaporate the solution with the aid of a current of air to dryness about 35˚. Dissolve the residue in 8 to 10 ml of ether, and then chill in an ice bath, if necessary, to induce crystallization. Collect the crystals on filter paper, wash with about 2 ml of cold ether, and allow to dry in air. The residue complies with the following test.

Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained with pentoxifylline RS or with the reference spectrum of pentoxifylline.

B. In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the principal peak in the chromatogram obtained with the reference solution (b).

Tests

Dissolution (2.5.2). Complies with the test stated under Tablets.

Chromatographic Purity. Determine by liquid chromatography (2.4.14), as described under Assay with the following modifications.

Test solution. Transfer a quantity of powder containing 40 mg of pentoxifylline to a 50.0-ml volumetric flask. Add 0.4 ml of methanol and swirl for at least 1 minute. Add about 30 ml of extracting solution and sonicate for 60 minutes with occasional swirling of the flask. Add an additional 15 ml of extracting solution, allow cooling to room temperature, diluting with extracting solution to volume, mix and centrifuging. Dilute 10.0 ml of this solution to a 25.0-ml volumetric flask, with extracting solution to volume and mix to obtain a solution containing 0.032 per cent w/v of pentoxifylline.

Reference solution. Dissolve an accurately weighed quantity of pentoxifylline RS in extracting solution containing an amount of methanol equal to 0.8 per cent of the total volume, and dilute with extracting solution to obtain a solution containing  0.000096 per cent w/v of pentoxfylline.

Inject the reference solution. The test is not valid unless the relative standard deviation is not more than 5.0 per cent.

Inject the reference solution and the test solution. Run the chromatogram five times the retention time of the principal peak. In the chromatogram obtained with the test solution the area of any secondary peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (0.3 per cent) and the sum of the areas of all the secondary peaks is not more than three times the area of the principal peak in the chromatogram obtained with the reference solution (1.0 per cent). 

Other tests. Comply with the tests stated under Tablets.

Assay. Determine by liquid chromatography (2.4.14).

Perchloric acid solution. Dissolve 1g of perchloric acid in 1000 ml of water and mix.

Extracting solution. A mixture of 70 volumes of water and 30 volumes of alcohol.

Test solution. Weigh and powder 20 tablets. Transfer a quantity of powder containing 40 mg of Pentoxifylline to a 50-ml volumetric flask. Add 0.4 ml of methanol, and swirl for at least 1 minute. Add about 30 ml of extracting solution, and sonicate for 60 minutes with occasional swirling of the flask. Add an additional 15 ml of extracting solution, allow cooling to room temperature, diluting with extracting solution to volume and mix and centrifuging Dilute 3.0 ml of this solution to 50.0 ml with extracting solution.

Reference solution (a). Dissolve 20 mg of pentoxifylline  RS and 10 mg of caffeine RS to 25-ml volumetric flask, in 0.2 ml of methanol, and dilute with extracting solution to volume, and mix. Dilute 3.0 ml of this solution into a 50-ml volumetric flask, dilute with extracting solution to volume and mix.

Reference solution (b). Dissolve a quantity of pentoxifylline RS in extracting solution containing an amount of methanol equal to 0.8 per cent of the total volume and dilute with extracting solution to obtain a solution containing  0.0048 per cent w/v of pentoxfylline.

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 80 volumes of perchloric acid solution,15 volumes of acetonitrile, 2.5 volumes of tetrahydrofuran and 2 volumes of methanol.

     –   flow rate: 0.7 ml per minute,

     –   spectrophotometer set at 273 nm,

     –   injection volume: 10 µl.

Inject reference solution (a) and (b). The test is not valid unless the resolution between pentoxifylline and caffeine is not less than 10 obtained with reference solution (a) and the relative standard deviation for replicate injections is not more than 2.0 per cent obtained with reference solution (b).

Inject the reference solution (b) and the test solution.

Calculate the content of C13H18N₄O3.in the tablets.

Storage. Store protected from light and moisture, at a temperature not exceeding 30°.