Clomifene Tablets

General Notices

Action and use

Estrogen receptor modulator.

Definition

Clomifene Tablets contain Clomifene Citrate.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of clomifene citrate, C26H28ClNO,C6H8O7

92.5 to 107.5% of the stated amount.

Identification

A. The light absorption, Appendix II B, in the range 220 to 350 nm of the solution obtained in the Assay exhibits two maxima, at 235 nm and 292 nm.
B. Dissolve a quantity of the powdered tablets containing 5 mg of Clomifene Citrate in 5 mL of a mixture of 1 volume of acetic anhydride and 5 volumes of pyridine and heat in a water bath. A dark red colour is produced.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a sample of the medium and filter.
(2) Measure the absorbance of a layer of suitable thickness of the filtered sample, suitably diluted, if necessary, with 0.1m hydrochloric acid, at the maximum at 232 nm, Appendix II B.
determination of content

Calculate the total content of clomifene citrate, C26H28ClNO,C6H8O7, in the medium taking 317 as the value of A(1%, 1 cm) at the maximum at 232 nm.

Z-Isomer

Carry out the method for liquid chromatography, Appendix III D, using the following solution.

(1) Shake a quantity of the powdered tablets containing 50 mg of Clomifene Citrate with 50 mL of 0.1m hydrochloric acid for 10 minutes and filter. To 25 mL of the filtrate add 5 mL of 1m sodium hydroxide and extract with three 25-mL quantities of ethanol-free chloroform. Wash the combined extracts with 10 mL of water, dry over anhydrous sodium sulfate and add sufficientethanol-free chloroform to produce 100 mL. To 20 mL of the solution add 0.1 mL of triethylamine and sufficient hexane to produce 100 mL.
chromatographic conditions
(a) Use a stainless steel column (30 cm × 4 mm) packed with silica gel for chromatography (10 µm) (Porasil is suitable).
(b) Use isocratic elution and the mobile phase described below. Pass the mobile phase through the system until stabilisation is achieved (about 250 mL).
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 302 nm.
(f) Inject 20 µL of the solution.
(g) In the chromatogram obtained with the solution being examined, the peak due to E-clomifene precedes the peak due to Z-clomifene.
mobile phase

A mixture of ethanol-free chloroform and hexane, each containing 0.10% v/v of triethylamine, adjusted so that baseline separation is obtained between E- and Z-clomifene (20 volumes of ethanol-free chloroform and 80 volumes of hexane is usually suitable).

system suitability

The test is not valid unless baseline separation is achieved between E- and Z-clomifene and the column efficiency is greater than 10,000 theoretical plates per metre determined using the peak due to the E-isomer.

limits

30.0 to 50.0% of the content of clomifene citrate as determined in the Assay.

Calculate the percentage of Z-isomer from the expression 100AZ/(1.08AD+ AZ) where AZ and AD are the areas of the peaks due to the Z- and E-isomers, respectively.

Assay

Weigh and powder 20 tablets. Shake a quantity of the powder containing 50 mg of Clomifene Citrate for 30 minutes with 70 mL of 0.1m hydrochloric acid prepared using a 30% v/v solution of propan-2-ol as solvent, dilute to 100 mL with the propanolic hydrochloric acid and filter. Dilute 5 mL of the filtrate to 100 mL with 0.1m hydrochloric acid and measure the absorbance of the resulting solution at the maximum at 292 nm, Appendix II B, using in the reference cell a solution prepared by diluting 5 mL of the propanolic hydrochloric acid to 100 mL with 0.1m hydrochloric acid. Calculate the content of C26H28ClNO,C6H8O7 taking 175 as the value of A(1%, 1 cm) at the maximum at 292 nm.

Storage

Clomifene Tablets should be protected from light.