Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Fibrate lipid-regulating drug.
DEFINITION
Gemfibrozil Capsules contain Gemfibrozil.
The capsules comply with the requirements stated under Capsules and with the following requirements.
Content of gemfibrozil, C₁₅H₂₂O₃:
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the contents of the capsules containing about 0.5 g of Gemfibrozil with 10 mL of n-hexane for 10 minutes, filter through a filter paper previously washed with 20 mL of n-hexane, evaporate the filtrate to dryness on a water bath and then dry over silica gel at a pressure of 2 kPa for 2 hours or until a waxy solid is obtained.
The infrared absorption spectrum of the 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
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.
Measure the absorbance of a suitable solution of gemfibrozil BPCRS, adding the minimum volume of 0.1M sodium hydroxide, if necessary, to complete dissolution, 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 contents of the capsules containing 0.4 g of Gemfibrozil with 100 mL of methanol and filter
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase and further dilute 1 volume of this solution to 5 volumes with the mobile phase.
(3) 0.0004% w/v of gemfibrozil impurity E BPCRS in the 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 any 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
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 50 mL of methanol to a quantity of the mixed contents of 20 capsules containing 0.15 g of Gemfibrozil, shake on a mechanical shaker for 10 minutes, add 20 mL of water, 1 mL of glacial acetic acid and sufficient methanol to produce 100 mL, mix and filter (Whatman GF/C paper is suitable), discarding the first 20 mL of filtrate. Dilute 1 volume of the filtrate to 5 volumes with the mobile phase.
(2) Dissolve 30 mg of gemfibrozil BPCRS in 80 mL of methanol, add 1 mL of glacial acetic acid and dilute to 100 mL with water.
(3) 0.01% w/v of gemfibrozil methyl ester BPCRS in a solution prepared by diluting 1 volume of solution (1) to 3 volumes with the 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.
(c) Use a flow rate of 1 mL per minute.
(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.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to gemfibrozil and gemfibrozil methyl ester is at least 4.0.
DETERMINATION OF CONTENT
Calculate the content of C₁₅H₂₂O₃ in the capsules from the chromatograms obtained using the declared content of C₁₅H₂₂O₃ in gemfibrozil BPCRS.
