Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Fibrate; lipid-regulating drug.
DEFINITION
Fenofibrate Tablets contain Fenofibrate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of fenofibrate, C20H21ClO4
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Disperse a quantity of the powdered tablets containing 0.2 g of Fenofibrate in 20 mL of acetone, filter through a 0.45-μm nylon syringe filter and evaporate to dryness under a stream of nitrogen. Add 5 mL of water to the residue and mix with the aid of ultrasound. Filter the suspension and dry the resulting powder at 60° at a pressure of 1 kPa for 30 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of fenofibrate (RS 511).
TESTS
Dissolution
Comply with 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 0.05M sodium lauryl sulfate, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with 0.025M sodium dodecyl sulfate, if necessary, to produce a solution expected to contain 0.0074% w/v of Fenofibrate.
(2) 0.0074% w/v of fenofibrate BPCRS in 0.025M sodium dodecyl sulfate.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.0 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Hypersil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 286 nm.
(f) Inject 5 μL of each solution.
MOBILE PHASE
30 volumes of water previously adjusted to pH 2.5 with orthophosphoric acid and 70 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the retention time of fenofibrate is about 10 minutes.
DETERMINATION OF CONTENT
Calculate the total content of fenofibrate, C20H21ClO4, in the medium from the chromatograms obtained and using the declared content of C20H21ClO4 in fenofibrate BPCRS.
LIMITS
The amount of fenofibrate released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Fenofibrate with 80 mL of the mobile phase, mix with the aid of ultrasound and intermittent shaking. Dilute to 100 mL, mix and filter (a 0.45-μm nylon syringe filter is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes. Further dilute 1 volume to 5 volumes.
(3) 0.0001% w/v each of fenofibrate impurity A EPCRS and fenofibrate impurity B EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 20 μL. Allow the chromatography to proceed for twice the retention time of fenofibrate.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to fenofibrate (retention time about 10 minutes) are: impurity A, about 0.34 and impurity B, about 0.36.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and impurity B is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any 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 is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Fenofibrate with 80 mL of the mobile phase, mix with the aid of ultrasound and intermittent shaking. Dilute to 100 mL, mix and filter (a 0.45-μm nylon syringe filter is suitable).
(2) 0.1% w/v of fenofibrate BPCRS.
(3) 0.0001% w/v each of fenofibrate impurity A EPCRS and fenofibrate impurity B EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 10 μL.
SYSTEM SUITABILITY
The Assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and impurity B is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C20H21ClO4 in the tablets from the chromatograms obtained and using the declared content of C20H21ClO4 in fenofibrate BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Fenofibrate.
