Cortisone Tablets

General Notices

Action and use

Corticosteroid.

Definition

Cortisone Tablets contain Cortisone Acetate in fine powder.

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

Content of cortisone acetate, C23H30O6

90.0 to 110.0% of the stated amount.

Identification

Extract a quantity of the powdered tablets containing 0.1 g of Cortisone Acetate with 5 mL of chloroform, filter and evaporate the chloroform. The residue complies with the following tests.

A. The infrared absorption spectrum, Appendix II A, is concordant with a spectrum prepared from the residue obtained by evaporating 5 mL of a 2% w/v solution of cortisone acetate BPCRS in chloroform. Use the same method of evaporation of the chloroform as that for the tablet extract. Prepare potassium bromide discs.
B. Complies with the test for identification of steroids, Appendix III A, using impregnating solvent I and mobile phase B.

Tests

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared immediately before use.

(1) Mix a quantity of the powdered tablets containing 25 mg of Cortisone Acetate with 10 mL of the mobile phase, place in an ultrasonic bath for 10 minutes and filter (Whatman GF/C filter is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(3) 0.002% w/v each of cortisone acetate BPCRS and hydrocortisone acetate BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 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) Continue the chromatography for twice the retention time of the principal peak.

mobile phase

Mix 400 mL of acetonitrile with 550 mL of water, allow to equilibrate and adjust the volume to 1000 mL with water.

system suitability

Equilibrate the column with the mobile phase at a flow rate of 1 mL per minute for about 30 minutes.

Inject solution (3). When the chromatograms are recorded in the prescribed conditions the retention times are: hydrocortisone acetate, about 10 minutes and cortisone acetate, about 12 minutes.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to hydrocortisone acetate and cortisone acetate is at least 4.2; if necessary, adjust the concentration of acetonitrile in the mobile phase.

limits

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%).

Disregard any peak with an area less than 0.05 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

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 50 revolutions per minute.
(b) Use 900 mL of a 0.3% w/v solution of sodium dodecyl sulfate, at a temperature of 37°, as the medium.
procedure
(1) After 45 minutes withdraw a 10 mL sample of the medium and measure the absorbance of the filtered sample at the maximum at 242 nm, Appendix II B using a 0.3% w/v solution of sodium dodecyl sulfate in the reference cell.
(2) Measure the absorbance of a 0.0028% w/v solution of cortisone acetate BPCRS using a 0.3% w/v solution of sodium dodecyl sulfate in the reference cell.
determination of content

Calculate the total content of C23H30O6, in the medium from the absorbances obtained and using the declared content of C23H30O6, in cortisone acetate BPCRS.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Dilute 50 mL of a solution in methanol containing 0.02% w/v each of cortisone acetate BPCRS and prednisolone to 100 mL with water.
(2) Add 50 mL of methanol to a quantity of the powdered tablets containing 10 mg of Cortisone Acetate, shake, mix with the aid of ultrasound for 2 minutes, dilute to 100 mL with water, shake, centrifuge and use the supernatant liquid.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil ODS 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 240 nm.
(f) Inject 20 µL of each solution.
mobile phase

40 volumes of water and 60 volumes of methanol.

system suitability

The Assay is not valid unless, in the chromatogram obtained with solution (1), the resolution factor between the peaks due to cortisone acetate and prednisolone is at least 5.0.

determination of content

Calculate the content of C23H30O6 in the tablets using the declared content of C23H30O6 in cortisone acetate BPCRS.

Storage

Cortisone Tablets should be protected from light.