Edition: BP 2025 (Ph. Eur. 11.6 update)
Prolonged-release Alfuzosin Tablets
Alfuzosin 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
Alpha1-adrenoceptor antagonist.
DEFINITION
Alfuzosin Prolonged-release Tablets contain Alfuzosin Hydrochloride. 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 alfuzosin hydrochloride. 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 alfuzosin hydrochloride, C19H27N5O4,HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
Shake a quantity of the powdered tablets containing 30 mg of Alfuzosin Hydrochloride with 250 mL of water for 5 minutes and filter. Adjust the pH of the filtrate to pH 12.5 with 18M ammonia, extract with two 25-mL quantities of dichloromethane, wash the combined extracts with 10 mL of water, dry over sodium sulfate and evaporate to dryness. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of alfuzosin (RS 446).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of powdered tablets containing 15 mg of Alfuzosin Hydrochloride in 70 mL of methanol for 30 minutes, add 10 mL of 0.01M hydrochloric acid, cool, dilute to 100 mL with methanol and filter. Dilute 1 volume of the solution to 5 volumes with the mobile phase.
(2) Dilute 1 volume of solution (1) to 200 volumes with the mobile phase.
(3) Dilute 2 volumes of solution (2) to 5 volumes with the mobile phase.
(4) Dilute 1 volume of solution (2) to 5 volumes with the mobile phase.
(5) 0.01% w/v of alfuzosin impurity standard BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Inertsil ODS 2 is suitable).
(b) Use isocratic elution and 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 254 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1), allow the chromatography to proceed for twice the retention time of the principal peak.
MOBILE PHASE
1 volume of tetrahydrofuran, 20 volumes of acetonitrile and 80 volumes of sodium perchlorate solution prepared in the following manner. Add 5 mL of perchloric acid to 900 mL of water, adjust to pH 3.5 with 2M sodium hydroxide and add sufficient water to produce 1000 mL.
SYSTEM SUITABILITY
The test is not valid unless:
the chromatogram obtained with solution (5) closely resembles the reference chromatogram supplied with alfuzosin impurity standard BPCRS;
the resolution between the peaks due to impurity D and impurity E is at least 2.0;
the resolution between the peaks due to alfuzosin and impurity A is at least 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity D (the first eluting peak in the chromatogram obtained with solution (5)) is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to impurity E (the second eluting peak in the chromatogram obtained with solution (5)) is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.2%);
the sum of the areas of any other secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D using the following solutions in the mobile phase.
(1) Weigh and powder 20 tablets. Shake a quantity of powdered tablets containing 10 mg of Alfuzosin Hydrochloride in 70 mL of methanol for 30 minutes, add 10 mL of 0.01M hydrochloric acid, cool, dilute to 100 mL with methanol and filter. Dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.
(2) 0.001% w/v of alfuzosin hydrochloride BPCRS.
(3) 0.01% w/v of alfuzosin impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The Assay is not valid unless:
the chromatogram obtained with solution (3) closely resembles the reference chromatogram supplied with alfuzosin impurity standard BPCRS;
the resolution between the peaks due to impurity D and impurity E is at least 2.0;
the resolution between the peaks due to alfuzosin and impurity A is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C19H27N5O4 ,HCl in the tablets from the chromatograms obtained and using the declared content of C19H27N5O4,HCl in alfuzosin hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Alfuzosin Hydrochloride.
