Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Histamine H1 receptor antagonist; antihistamine.
DEFINITION
Fexofenadine Tablets contain Fexofenadine Hydrochloride. They may be coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
PRODUCTION
The manufacturing process of Fexofenadine Hydrochloride, used in the formulation of Fexofenadine Tablets, is validated to ensure that the content of the enantiomer impurity B is not more than 0.1%.
Content of fexofenadine hydrochloride, C32H39NO4,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 30 mg of Fexofenadine Hydrochloride with 10 mL of methanol for 5 minutes, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of fexofenadine hydrochloride (RS 459).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
(a) Use Apparatus 2, rotating the paddle at 50 revolutions per minute.
(b) Use 900 mL of 0.001M hydrochloric acid, 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 0.001M hydrochloric acid if necessary, to produce a solution expected to contain 0.003% w/v of Fexofenadine Hydrochloride.
(2) 0.003% w/v of fexofenadine hydrochloride BPCRS in 0.001M hydrochloric acid.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
DETERMINATION OF CONTENT
Calculate the total content of fexofenadine hydrochloride, C32H39NO4,HCl, in the medium from the chromatograms obtained and using the declared content of C32H39NO4,HCl in fexofenadine hydrochloride BPCRS.
LIMITS
The amount of fexofenadine hydrochloride 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 in solvent A.
SOLVENT A
Equal volumes of acetonitrile and a buffer solution containing 0.05M sodium dihydrogen orthophosphate monohydrate and 0.006M sodium perchlorate. The pH of the buffer solution is adjusted to 2.0 with orthophosphoric acid before the addition of acetonitrile.
(1) Shake a quantity of powdered tablets containing 25 mg of Fexofenadine Hydrochloride with 25 mL of solvent A and filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with solvent A and further dilute 1 volume of the resulting solution to 5 volumes with solvent A.
(3) 0.1% w/v of fexofenadine impurity standard BPCRS in solvent A.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with phenylsilyl silica gel for chromatography (5 μm) (Zorbax SB Phenyl is suitable).
(b) Use isocratic elution using the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 220 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
350 volumes of acetonitrile and 650 volumes of a buffer solution containing 0.05M sodium dihydrogen orthophosphate monohydrate and 0.006M sodium perchlorate the pH of which is adjusted to 2.0 with orthophosphoric acid. To the resulting solution add 3 volumes of triethylamine and mix.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the principal peaks due to Fexofenadine and impurity A is at least 10.
LIMITS
In the chromatogram obtained with solution (1):
multiply the peak area of any peak corresponding to impurity A by 1.4;
the area of any secondary peak corresponding to impurity A is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.6%);
the area of any secondary peak corresponding to impurity C is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
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 all secondary peaks is not greater than 5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
Disregard any peak with an area less than 0.5 times 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.
(1) Shake a quantity of powdered tablets containing 50 mg of Fexofenadine Hydrochloride with 50 mL of solvent A and filter.
(2) 0.1% w/v of fexofenadine hydrochloride BPCRS in solvent A.
(3) 0.1% w/v of fexofenadine impurity standard BPCRS in solvent A.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the principal peaks due to Fexofenadine and impurity A is at least 10.
DETERMINATION OF CONTENT
Calculate the content of C32H39NO4,HCl in the tablets using the declared content of C32H39NO4,HCl in fexofenadine hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A and C listed under Fexofenadine Hydrochloride.
