- British Pharmacopoeia Volume III
- Formulated Preparations: Specific Monographs
Cyproterone Tablets |
Antiandrogen.
Cyproterone Tablets contain Cyproterone Acetate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
95.0 to 105.0% of the stated amount.
A. Shake a quantity of the powdered tablets containing 0.1 g of cyproterone acetate with 20 mL of dichloromethane, filter through a glass-fibre filter paper (Whatman GF/C is suitable) and evaporate the filtrate to dryness using a rotary evaporator and a water bath at 40°. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of cyproterone acetate (RS 395).
B. In the Assay, the chromatogram obtained with solution (2) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (1).
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. For tablets containing less than 100 mg of Cyproterone Acetate use as the medium 900 mL of a 0.07% w/v solution of sodium dodecyl sulfate in 0.1m hydrochloric acid. For tablets containing 100 mg or more of Cyproterone Acetate use as the medium 900 mL of a 0.10% w/v solution of sodium dodecyl sulfate in 0.1m hydrochloric acid. Rotate the paddle at 100 revolutions per minute. Withdraw a sample of 20 mL of the medium and filter. Measure the absorbance of the filtrate, Appendix II B, diluted with the dissolution medium if necessary, at the maximum at 285 nm using dissolution medium in the reference cell. Measure the absorbance of a suitable solution of cyproterone acetate BPCRS in the dissolution medium and calculate the total content of cyproterone acetate, C24H29ClO4, in the medium using the declared content of C24H29ClO4 in cyproterone acetate BPCRS.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Cyproterone Acetate with 50 mL of a 4:1 mixture of acetonitrile and water for 5 minutes, dilute to 100 mL with water and filter through a glass-fibre filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) Dilute 1 volume of a solution containing 0.01% w/v each of cyproterone acetate BPCRS and medroxyprogesterone acetate BPCRS in a 4:1 mixture of acetonitrile and water to 10 volumes with the mobile phase.
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (3 µm) (Spherisorb 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.
40 volumes of acetonitrile and 60 volumes of water.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 3.0.
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of all the secondary peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 50 mg of Cyproterone Acetate with 50 mL of a 4:1 mixture of acetonitrile and water for 5 minutes, dilute to 100 mL with the same solvent mixture and filter through a glass-fibre filter (Whatman GF/C is suitable); dilute 1 volume of the filtrate to 10 volumes with the mobile phase
(2) Dilute 1 volume of a 0.05% w/v solution of cyproterone acetate BPCRS in a 4:1 mixture of acetonitrile and water to 10 volumes with the mobile phase.
(3) Dilute 1 volume of a solution containing 0.01% w/v each of cyproterone acetate BPCRS and medroxyprogesterone acetate BPCRS in a 4:1 mixture of acetonitrile and water to 10 volumes with the mobile phase.
The chromatographic procedure described under Related substances may be used.
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 3.0.
Calculate the content of C24H29ClO4 in the tablets, using the declared content of C24H29ClO4 in cyproterone acetate BPCRS.
The impurities limited by the requirements of this monograph include those listed in the monograph for Cyproterone Acetate and the following:
A. 6β-Chloro-7α,17α-dihydroxy-1α,2α-methylenepregna-4-ene-3,20-dione (chlorohydrin derivative)
B. 17α-Hydroxy-6-chloro-1α-chloromethylpregna-4,6-diene-3,20-dione (1-chloromethyl derivative)
C. 1α,2α-Methylene-3,6,20-trioxopregna-4-en-17α-yl acetate
D. 17α-Hydroxy-6-chloro-1α,2α-methylenepregna-4,6-diene-3,20-dione (cyproterone)