Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Bezafibrate Prolonged-release Tablets from different manufacturers, whilst complying with the requirements of the monograph, are not interchangeable unless otherwise justified and authorised.
Action and use
Fibrate; lipid-regulating drug.
DEFINITION
Bezafibrate Prolonged-release Tablets contain Bezafibrate. They are formulated so that the medicament is released over a period of several hours.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of bezafibrate. The dissolution profile reflects the in vivo performance which in turn is compatible with the dosage schedule recommended by the manufacturer.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of bezafibrate, C19H20ClNO4
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 0.2 g of Bezafibrate with two 10-mL quantities of acetone for 10 minutes, filter the combined extracts (Whatman GF/C is suitable) and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of Bezafibrate (RS 419).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 100 mg of Bezafibrate with 15 mL of methanol for 2 minutes, shake for a further 10 minutes, cool, add sufficient mobile phase to produce 100 mL, mix and filter, discarding the first 20 mL of filtrate.
(2) Dilute 1 volume of solution (1) to 200 volumes with the mobile phase.
(3) Dissolve sufficient quantities of bezafibrate BPCRS and chlorobenzoyltyramine BPCRS in the minimum quantity of methanol and dilute with mobile phase to produce a solution containing 0.0002% w/v of bezafibrate BPCRS and 0.0002% w/v of chlorobenzoyltyramine BPCRS.
(4) Dilute 1 volume of solution (2) to 10 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm X 3.9 mm) packed with octadecylsilyl silica gel for chromatography (4 pm) (Novapak C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use ambient column temperature.
(e) Use a detection wavelength of 230 nm.
(f) Inject 20 pL of each solution.
The retention time of bezafibrate is about 5 minutes. Allow the chromatography to proceed for four times the retention time of the principal peak.
MOBILE PHASE
A mixture of 3.9 volumes of a 40% w/v solution of tetrabutylammonium hydroxide, 400 volumes of acetonitrile and 600 volumes of water, adjusting the final pH to 4.0 with 10% v/v orthophosphoric acid.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to bezafibrate and chlorobenzoyltyramine is at least 7.0. If necessary adjust the content of tetrabutylammonium hydroxide to obtain the required resolution.
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) (0.5%);
the total area of any such peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.75%).
Disregard any peak with an area less than that of the principal peak in the chromatogram obtained with solution (4) (0.01%).
ASSAY
Weigh and powder 20 tablets. For solution (1) mix with the aid of ultrasound a quantity of the powdered tablets containing 0.1 g of Bezafibrate with 70 mL of methanol for 2 minutes, shake for a further 10 minutes, cool, add sufficient methanol to produce 100 mL, mix and filter discarding the first 20 mL of filtrate. Dilute 1 volume to 100 volumes with methanol. Solution (2) is a 0.001% w/v solution of bezafibrate BPCRS in methanol.
Measure the absorbance of the resulting solutions at the maximum at about 230 nm, Appendix II B. Calculate the content of C19H20ClNO4 from the declared content of C19H20ClNO4 in bezafibrate BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include:
![4-chloroW-[2-(4-hydroxyphenyl)ethyl]benzamide (chlorobenzoyltyramine).](https://nhathuocngocanh.com/bp/wp-content/uploads/2025/09/bezafibrat-prolonged-release-tablets-1.jpg)
4-chloro-N-[2-(4-hydroxyphenyl)ethyl]benzamide (chlorobenzoyltyramine).
