Soluble Prednisolone Tablets
Action and use
Glucocorticoid.
DEFINITION
Prednisolone Soluble Tablets contain Prednisolone Sodium Phosphate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of prednisolone, C21H28O5
90.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Add a quantity of powdered tablets containing the equivalent of 7.5 mg of prednisolone to 10 mL of water, leave to stand for 30 minutes, swirl and filter.
(2) 0.1% w/v of prednisolone sodium phosphate BPCRS.
(3) Equal volumes of solutions (1) and (2).
(4) Equal volumes of solution (2) and a 0.1% w/v solution of betamethasone sodium phosphate BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254.
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, heat at 105° for 10 minutes and examine under ultraviolet light (254 nm).
MOBILE PHASE
33 volumes of water, 47 volumes of glacial acetic acid and 120 volumes of butan-1-ol, prepared immediately before use.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (4) shows two principal spots with almost identical Rf values.
CONFIRMATION
The chromatograms obtained with solutions (1), (2) and (3) show single principal spots with similar Rf values.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to prednisolone sodium phosphate in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the requirements 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 15 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with water if necessary, to produce a solution expected to contain the equivalent of 0.00055% w/v of prednisolone.
(2) 0.00074% w/v of prednisolone sodium phosphate BPCRS in water.
(3) 0.0006% w/v each of prednisolone sodium phosphate BPCRS and prednisolone BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Luna 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 an ambient column temperature.
(e) Use a detection wavelength of 247 nm.
(f) Inject 100 μL of each solution.
MOBILE PHASE
26 volumes of acetonitrile and 74 volumes of water containing 0.544% w/v of potassium dihydrogen orthophosphate and 0.240% w/v of hexylamine. When the chromatograms are recorded under the prescribed conditions, the relative retention with reference to prednisolone sodium phosphate (retention time about 6.5 minutes) of prednisolone is about 1.3.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone sodium phosphate and prednisolone is at least 4.5.
DETERMINATION OF CONTENT
Calculate the content of C21H28O5 (prednisolone) in the medium using the calculated content of C21H27Na2O8P in prednisolone sodium phosphate BPCRS. Each mg of C21H27Na2O8P is equivalent to 0.7440 mg of C21H28O5.
LIMITS
The amount of prednisolone released is not less than 75% (Q) of the stated amount.
Free prednisolone
In the test for Related substances, the area of any peak due to prednisolone in the chromatogram obtained with solution
(1) is not greater than the area of the principal peak in the chromatogram obtained with solution (5) (4%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add a quantity of powdered tablets containing the equivalent of 20 mg of prednisolone to 8 mL of the mobile phase, leave to stand for 30 minutes and swirl. Add sufficient mobile phase to produce 10 mL and filter.
(2) Dilute 1 volume of solution (1) to 50 volumes with the mobile phase.
(3) 0.004% w/v each of prednisolone sodium phosphate BPCRS and prednisolone BPCRS in the mobile phase.
(4) Dilute 1 volume of solution (2) to 20 volumes with the mobile phase.
(5) Dilute 1 volume of solution (1) to 25 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 20 μL. Allow the chromatography to proceed for 3 times the retention time of prednisolone sodium phosphate.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone sodium phosphate and prednisolone is at least 4.5.
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) (2%);
the area of not more than one secondary peak is greater than half the area of the principal peak in the chromatogram obtained with solution (2) (1%);
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) (3%).
Disregard any peak due to prednisolone and any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
ASSAY
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add a quantity of powdered tablets containing the equivalent of 5 mg of prednisolone to 5 mL of water, leave to stand for 30 minutes and swirl. Add sufficient water to produce 20 mL and filter.
(2) 0.034% w/v of prednisolone sodium phosphate BPCRS.
(3) 0.025% w/v each of prednisolone sodium phosphate BPCRS and prednisolone BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with an injection volume of 20 μL.
SYSTEM SUITABILITY
The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to prednisolone sodium phosphate and prednisolone is at least 4.5.
DETERMINATION OF CONTENT
Calculate the content of C21H28O5 (prednisolone) in the tablets using the calculated content of C21H27Na2O8P in prednisolone sodium phosphate BPCRS. Each mg of C21H27Na2O8P is equivalent to 0.7440 mg of C21H28O5.
STORAGE
Prednisolone Soluble Tablets should be protected from light.
LABELLING
The quantity of the active ingredient is stated in terms of the equivalent amount of prednisolone.
