Gemfibrozil Tablets

General Notices

Action and use

Fibrate lipid-regulating drug.

Definition

Gemfibrozil Tablets contain Gemfibrozil.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of gemfibrozil, C₁₅H₂₂O₃

95.0 to 105.0% of the stated amount.

Identification

Mix a quantity of the powdered tablets containing 0.3 g of Gemfibrozil with 10 mL of 0.1m sodium hydroxide, filter (Whatman 541 paper is suitable), acidify with a few drops of 2m sulfuric acid, shake and centrifuge. Wash the precipitate with water, allow to dry in air and dry over anhydrous silica gel at a pressure of 2 kPa for 4 hours. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of gemfibrozil (RS 167).

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions

(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.

(b) Use 900 mL of 0.2m phosphate buffer pH 7.5, at a temperature of 37°, as the medium.

procedure

(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, at the maximum at 276 nm, Appendix II B using 0.2m phosphate buffer pH 7.5 in the reference cell.

(2) Measure the absorbance of a suitable solution of gemfibrozil BPCRS prepared by dissolving the substance in the minimum volume of methanol and diluting with 0.2m phosphate buffer pH 7.5. and using 0.2m phosphate buffer pH 7.5 in the reference cell.

determination of content

Calculate the total content of gemfibrozil, C₁₅H₂₂O₃, in the medium from the absorbances obtained and using the declared content of C₁₅H₂₂O₃ in gemfibrozil BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 0.6 g of Gemfibrozil with 70 mL of methanol for 15 minutes, add sufficient methanol to produce 100 mL and filter.

(2) Dilute 1 volume of solution (1) to 100 volumes with mobile phase and further dilute 1 volume of this solution to 5 volumes with mobile phase.

(3) 0.0006% w/v of gemfibrozil impurity E BPCRS in mobile phase.

(4) 0.001% w/v of gemfibrozil methyl ester BPCRS and 0.0004% w/v of gemfibrozil impurity E BPCRS in solution (2).

chromatographic conditions

The chromatographic procedure described under Assay may be used. For solution (1) allow the chromatography to proceed for twice the retention time of the principal peak.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to gemfibrozil and gemfibrozil methyl ester is at least 4.0 and the resolution between the peaks due to gemfibrozil methyl ester and gemfibrozil impurity E is at least 1.2.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to gemfibrozil impurity E is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any secondary peaks other than the peak corresponding to gemfibrozil impurity E is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the powdered tablets containing 84 mg of Gemfibrozil with 80 mL of methanol (80%) on a mechanical shaker for 15 minutes, add sufficient methanol (80%) to produce 100 mL, mix and filter (Whatman 542 paper is suitable), discarding the first 20 mL of filtrate.

(2) 0.084% w/v of gemfibrozil BPCRS prepared by dissolving the substance in the minimum volume of methanol and diluting with methanol (80%).

(3) 0.01% w/v of gemfibrozil methyl ester BPCRS in a solution prepared by diluting 1 volume of solution (1) to 10 volumes with a mixture of 2 volumes of methanol and 3 volumes of mobile phase.

chromatographic conditions

(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Spherisorb ODS 2 or Regis C18 are suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 276 nm.

(f) Inject 20 µL of each solution.

mobile phase

1 volume of glacial acetic acid, 19 volumes of water and 80 volumes of methanol.