Prednisolone Tablets

General Notices

Action and use

Glucocorticoid.

Definition

Prednisolone Tablets contain Prednisolone.

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

Content of prednisolone, C21H28O5

90.0 to 110.0% of the stated amount.

Identification

Extract a quantity of the powdered tablets with acetone, filter and evaporate the filtrate to dryness. The residue complies with the following tests.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of prednisolone (RS 282).
B. Complies with the test for the Identification of steroids, Appendix III A, using impregnating solvent I and mobile phase A.

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 50 revolutions per minute.
(b) Use 900 mL of water, at a temperature of 37°, as the medium.
procedure

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

(1) After 45 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with water if necessary, expected to contain 0.0001% w/v of Prednisolone.
(2) Dilute 1 volume of a 0.1% w/v solution of prednisolone BPCRS in methanol to 1000 volumes with water.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
system suitability

The test is not valid unless, in the chromatogram obtained with solution (1), the column efficiency, determined using the peak due to prednisolone, is greater than 15,000 theoretical plates per metre.

determination of content

Calculate the total content of C21H28O5 in the medium from the chromatograms obtained and using the declared content of C21H28O5 in prednisolone BPCRS.

Related substances

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

(1) Shake a quantity of the powdered tablets containing 10 mg of Prednisolone with 25 mL of methanol for 10 minutes and mix with the aid of ultrasound for 2 minutes; filter the extract (Whatman GF/F is suitable), wash the filter with two 10 mL quantities of methanol, combine the filtrate and washings and evaporate to dryness using a rotary evaporator and a warm water bath; dissolve the residue in 10 mL of tetrahydrofuran and dilute to 20 mL with water.
(2) Dilute 1 volume of solution (1) to 100 volumes with a 50% v/v solution of tetrahydrofuran.
(3) 0.002% w/v each of prednisolone BPCRS and hydrocortisone 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) (Alltima C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 45°.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for 4.5 times the retention time of the principal peak.

In the chromatogram obtained with solution (3), the retention times are about 14 minutes and 15.5 minutes for prednisolone and hydrocortisone respectively.

mobile phase

Mix 220 volumes of tetrahydrofuran with 700 volumes of water, allow to equilibrate, dilute to 1000 volumes with water and mix.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone and hydrocortisone is at least 2.2. If necessary, adjust the concentration of tetrahydrofuran in the mobile phase.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%);

the sum of the areas of any secondary peaks is not greater than three times the area of the principal peak in the chromatogram obtained with solution (2) (3%).

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%) and any peak with a retention time of 3 minutes or less.

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Prednisolone comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Add 15 mL of the mobile phase to one tablet, mix with the aid of ultrasound for at least 10 minutes. Add sufficient of the mobile phase to produce a solution expected to contain 0.005% w/v of Prednisolone, centrifuge and use the supernatant liquid.
(2) 0.005% w/v of prednisolone BPCRS in a mixture of 58 volumes of methanol and 42 volumes of water.
(3) 0.0050% w/v of prednisolone BPCRS and 0.0075% w/v of dexamethasone BPCRS in the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 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.
mobile phase

42 volumes of water and 58 volumes of methanol.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone and dexamethasone is greater than 2.5.

determination of content

Calculate the content of C21H28O5 in each tablet using the declared content of C21H28O5 in prednisolone BPCRS.

Assay

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

(1) Add 58 mL of methanol to a quantity of the powder containing 5 mg of Prednisolone, shake for 10 minutes, add sufficient water to produce 100 mL, mix and filter.
(2) 0.005% w/v of prednisolone BPCRS in a mixture of 58 volumes of methanol and 42 volumes of water.
(3) 0.005% w/v of prednisolone BPCRS and 0.0075% w/v of dexamethasone BPCRS in a mixture of 58 volumes of methanol and 42 volumes of water.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
system suitability

The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone and dexamethasone is greater than 2.5.

determination of content

Calculate the content of C21H28O5 in the tablets using the declared content of C21H28O5 in prednisolone BPCRS.

Storage

Prednisolone Tablets should be protected from light.