Griseofulvin Tablets

General Notices

Action and use

Antifungal.

Definition

Griseofulvin Tablets contain Griseofulvin.

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

Content of griseofulvin, C₁₇H₁₇ClO₆

95.0 to 105.0% of the stated amount.

Identification

A. Extract a quantity of the powdered tablets containing 0.125 g of Griseofulvin with 20 mL of chloroform, add 1 g of anhydrous sodium sulfate, shake and filter. Evaporate the filtrate to dryness and dry at a pressure not exceeding 0.7 kPa for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of griseofulvin (RS 172).

B. Shake a quantity of the powdered tablets containing 80 mg of Griseofulvin with 150 mL of ethanol (96%) for 20 minutes. Dilute to 200 mL with ethanol (96%) and filter. Dilute 2 mL of the filtrate to 100 mL with ethanol (96%). The light absorption of the resulting solution, Appendix II B, in the range 240 to 400 nm, exhibits two maxima at 291 nm and 325 nm and a shoulder at 250 nm.

C. Dissolve 5 mg of the powdered tablets in 1 mL of sulfuric acid and add 5 mg of powdered potassium dichromate. A 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 2, rotating the paddle at 100 revolutions per minute.

(b) Use 1000 mL of a 1.5% w/v solution of sodium dodecyl sulfate, at a temperature of 37°, as the medium.

procedure

After 45 minutes withdraw a 10 ml sample of the medium and filter. Measure the absorbance of the filtrate, suitably diluted if necessary with methanol (80%), at the maximum at 291 nm, Appendix II B, using a 1.5% w/v solution of sodium dodecyl sulfate in the reference cell.

determination of content

Calculate the total content of griseofulvin, C₁₇H₁₇ClO₆, in the medium taking 725 as the value of A(1%, 1 cm) at the maximum at 291 nm.

Related substances

Carry out the method for gas chromatography, Appendix III B, using the following solutions. Dissolve 50 mg of 9,10-diphenylanthracene (internal standard) in sufficient chloroform to produce 50 mL (solution A).

(1) Add 60 mL of chloroform to a quantity of the powdered tablets containing 50 mg of Griseofulvin, heat at 60° with shaking for 20 minutes, cool and dilute to 100 mL with chloroform. Centrifuge and evaporate 20 mL of the clear supernatant liquid to about 1 mL.

(2) Prepare solution (2) in the same manner as solution (1) but adding 1 mL of solution A before diluting to 100 mL with chloroform.

(3) Dissolve 5 mg of griseofulvin BPCRS in chloroform, add 2 mL of solution A and sufficient chloroform to produce 200 mL. Evaporate 20 mL of the solution to about 1 mL.

chromatographic conditions

(a) Use a glass column (1 m × 4 mm) packed with acid-washed, silanised diatomaceous support (100 to 120 mesh) coated with 1% w/w of cyanopropylmethyl phenylmethyl silicone fluid (OV 225 is suitable).

(b) Use nitrogen as the carrier gas at a flow rate of 50 to 60 mL per minute.

(d) Use an inlet temperature of 270°.

(e) Use a flame ionisation detector at a temperature of 300°.

(f) Inject a suitable volume of each solution.

(g) For solution (1), allow the chromatography to proceed for 3 times the retention time of griseofulvin.

When the chromatograms are recorded under the prescribed conditions the retention time of griseofulvin is about 11 minutes. The retention times relative to griseofulvin are: dechlorogriseofulvin, about 0.6; dehydrogriseofulvin, about 1.4.

limits

Using the chromatogram obtained with solution (3), calculate the ratio (R) of the area of the peak due to griseofulvin to the area of the peak due to the internal standard.

In the chromatogram obtained with solution (2):

the ratio of the area of any peak due to dechlorogriseofulvin to the area of the peak due to the internal standard is not greater than 0.6R (3%);

the ratio of the area of any peak due to dehydrogriseofulvin to the area of the peak due to the internal standard is not greater than 0.15R (0.75%).

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 35 mg of Griseofulvin add 60 mL of ethyl acetate, mix and heat to 60° with shaking for 20 minutes. Allow to cool and dilute to 100 mL with ethyl acetate. Centrifuge and transfer two 5 mL aliquots of the clear supernatant liquid into separate 100 mL graduated flasks. Add 5 mL of 2m methanolic methanesulfonic acid to the first flask, allow to stand at 20° for 30 minutes and dilute to 100 mL with methanol (solution A). Dilute the contents of the second flask to 100 mL with methanol (solution B). To a third flask add 5 mL of 2m methanolic methanesulfonic acid and dilute to 100 mL with methanol (solution C). Measure the absorbance of each solution at 266 nm, Appendix II B. Calculate the content of C₁₇H₁₇ClO₆ from the difference between the absorbance obtained with solution A and the sum of the absorbances obtained with solutions B and C and from the difference obtained by repeating the operation using 35 mg of griseofulvin BPCRS in place of the powdered tablets and from the declared content of C₁₇H₁₇ClO₆ in griseofulvin BPCRS.