Edition: BP 2025 (Ph. Eur. 11.6 update)
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
Extract a quantity of the powdered tablets containing 0.125 g of Griseofulvin with 20 mL of dichloromethane, 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).
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°C, 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.
LIMITS
The amount of griseofulvin released is not less than 75% of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase B.
(1) Disperse a quantity of powdered tablets containing 0.25 g of Griseofulvin in mobile phase B and dilute to 500 mL.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) 0.05% w/v of griseofulvin for system suitability EPCRS.
CHROMATOGRAPHIC CONDITIONS
a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Discovery C18 is suitable).
b) Use gradient elution and the mobile phase described below.
c) Use a flow rate of 1.0 mL per minute.
d) Use a column temperature of 30°C.
e) Use a detection wavelength of 290 nm.
f) Inject 10 µL of each solution.
MOBILE PHASE
Mobile phase A Mobile phase B
Composition 20 volumes of 0.1% v/v formic acid adjusted to pH 4.5 with dilute ammonia R2 and 80 volumes of water 15 volumes of water, 20 volumes of 0.1% v/v formic acid adjusted to pH 4.5 with dilute ammonia R2 and 65 volumes of acetonitrile
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
|---|---|---|---|
| 0–3 | 50 | 50 | isocratic |
| 3–13 | 50→40 | 50→60 | linear gradient |
| 13–16 | 40→10 | 60→90 | linear gradient |
| 16–24 | 10 | 90 | isocratic |
When the chromatograms are recorded under the prescribed conditions, the relative retention times with reference to griseofulvin (retention time about 16 minutes) are:
impurity A, about 0.4
impurity B, about 0.7
impurity C, about 1.1
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the peak-to-valley ratio is at least 3.0, where Hp is the height above the baseline of the peak due to impurity C and Hv is the height above the baseline of the lowest point of the curve separating this peak from the peak due to griseofulvin.
LIMITS
Identify any peak corresponding to impurity A in the chromatogram obtained with solution (1) and multiply the area of this peak by a correction factor of 0.6.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity B is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (3.0%);
the area of any peak corresponding to impurity A is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (2.0%);
the area of any peak corresponding to impurity C is not greater than 0.75 times the area of the principal peak in the chromatogram obtained with solution (2) (0.75%);
the area of any other secondary peak is not greater than 0.2 times 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 five times the area of the principal peak in the chromatogram obtained with solution (2) (5.0%).
Disregard any peak with an area less than 0.1 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) Disperse a quantity of powdered tablets containing 0.25 g of Griseofulvin in mobile phase B and dilute to 500 mL.
(2) 0.05% w/v of griseofulvin for LC assay and identification EPCRS.
The chromatographic conditions described under Related substances may be used.
DETERMINATION OF CONTENT
Calculate the content of C₁₇H₁₇ClO₆ in the tablets from the chromatograms obtained and using the declared content of C₁₇H₁₇ClO₆ in griseofulvin EPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Griseofulvin.
