Orodispersible Sildenafil Films
Action and use
Selective inhibitor of cyclic GMP specific phosphodiesterase (Type V) with vasodilator action; treatment of male erectile dysfunction.
DEFINITION
Sildenafil Orodispersible Films contain Sildenafil Citrate.
The films comply with the requirements stated under Oromucosal Preparations and with the following requirements.
Content of sildenafil, C22H30N6O4S
95.0 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) Shake a quantity of orodispersible films containing the equivalent of 25 mg of sildenafil with 10 mL of methanol and filter.
(2) 0.35% w/v of sildenafil citrate EPCRS in methanol.
(3) Equal volumes of solutions (1) and (2).
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 8 cm.
(e) After removal of the plate, dry in a current of warm air and examine under ultraviolet light (254 nm).
MOBILE PHASE
4 volumes of methanol and 8 volumes of ethyl acetate.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows a single spot with the same retention and colour to solution (2).
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of 0.01M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 15 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium, if necessary, to produce a solution containing the equivalent of 0.0027% w/v of sildenafil, at the maximum at 290 nm using 0.01M hydrochloric acid in the reference cell, Appendix II B.
(2) Measure the absorbance of a 0.0038% w/v solution of sildenafil citrate EPCRS in 0.01M hydrochloric acid at the maximum at 290 nm using 0.01M hydrochloric acid in the reference cell.
DETERMINATION OF CONTENT
Calculate the total content of sildenafil, C22H30N6O4S, in the medium using the declared content of sildenafil citrate, C28H38N6O11S, in sildenafil citrate EPCRS. Each mg of C28H38N6O11S is equivalent to 0.7118 mg of C22H30N6O4S.
LIMITS
The amount of sildenafil released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse a quantity of orodispersible films containing the equivalent of 100 mg of sildenafil in 10 mL of water. Dilute to 100 mL with acetonitrile and filter. Dilute 1 volume of this solution to 2 volumes with the mobile phase.
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase, further dilute 1 volume of this solution to 5 volumes with the same solvent.
(3) Dissolve 70 mg of sildenafil citrate EPCRS in 1 mL of a mixture containing 1 volume of formic acid and 2 volumes of hydrogen peroxide solution (100 vol) and allow to stand for 10 minutes. Dilute 1 volume of this solution to 250 volumes with the mobile phase (in-situ degradation of sildenafil to produce impurity B).
(4) 0.000075% w/v of sildenafil impurity A EPCRS in the mobile phase.
(5) Dilute 2.5 volumes of solution (2) to 10 volumes with the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 3.9 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Waters Symmetry C18 is suitable).
(b) Use isocratic elution and the mobile phases described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 30°.
(e) Use a detection wavelength of 290 nm.
(f) Inject 20 μL of each solution.
(g) Allow the chromatography to proceed for twice the retention time of sildenafil.
MOBILE PHASE
17 volumes of acetonitrile, 25 volumes of methanol and 58 volumes of a 0.7% v/v solution of triethylamine previously adjusted to pH 3.0 with orthophosphoric acid.
When the chromatograms are recorded under the prescribed conditions the retention time relative to sildenafil (retention time about 7 minutes) of impurity B is about 1.2.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to sildenafil and impurity B is at least 2.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak due to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (0.15%);
the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of impurities is not greater than 0.50%;
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Disperse ten films in the minimum volume of water possible (not exceeding 10% of the overall solvent mixture) and add sufficient acetonitrile to produce a solution expected to contain the equivalent of 0.1% w/v of sildenafil and filter. Dilute 1 volume of this solution to 50 volumes with mobile phase.
(2) 0.0028% w/v of sildenafil citrate EPCRS in the mobile phase.
(3) Dissolve 70 mg of sildenafil citrate EPCRS in 1 mL of a mixture containing 1 volume of formic acid and 2 volumes of hydrogen peroxide solution (100 vol) and allow to stand for 10 minutes. Dilute the resulting solution to 250 mL with the mobile phase (in-situ degradation of sildenafil to produce impurity B).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to sildenafil and impurity B is at least 2.5.
DETERMINATION OF CONTENT
Calculate the content of sildenafil, C22H30N6O4S, in the orodispersible films using the declared content of sildenafil citrate, C28H38N6O11S, in sildenafil citrate EPCRS. Each mg of C28H38N6O11S is equivalent to 0.7118 mg of C22H30N6O4S.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Sildenafil Citrate.
