Flumethasone Pivalate Cream
»Flumethasone Pivalate Cream contains not less than 90.0percent and not more than 110.0percent of the labeled amount of flumethasone pivalate (C27H36F2O6)in a suitable cream base.
Packaging and storage—
Preserve in collapsible tubes.
Identification—
Place a quantity of Cream,equivalent to about 400µg of flumethasone pivalate,in a 50-mLcentrifuge tube,and treat as directed in the Assay,collecting the extracts in a 50-mLcentrifuge tube.Evaporate the acetonitrile on a water bath (about 75
)with the aid of a stream of nitrogen.Dissolve the residue in 2.0mLof acetonitrile with the aid of heat,allow to cool,and centrifuge.Apply 50µLof this solution and 50µLof a solution of chloroform and methanol (1:1)of USP Flumethasone Pivalate RScontaining 200µg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in toluene until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Redevelop the plate in the same manner in a solvent system consisting of toluene and ethyl acetate (7:3),remove the plate from the developing chamber,and allow the solvent to evaporate.Locate the spots on the plate by examination under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
)with the aid of a stream of nitrogen.Dissolve the residue in 2.0mLof acetonitrile with the aid of heat,allow to cool,and centrifuge.Apply 50µLof this solution and 50µLof a solution of chloroform and methanol (1:1)of USP Flumethasone Pivalate RScontaining 200µg per mLto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in toluene until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Redevelop the plate in the same manner in a solvent system consisting of toluene and ethyl acetate (7:3),remove the plate from the developing chamber,and allow the solvent to evaporate.Locate the spots on the plate by examination under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Microbial limits á61ñ—
It meets the requirements of the tests for absence of Staphylococcus aureusand Pseudomonas aeruginosa.
Minimum fill á755ñ:
meets the requirements.
Assay—
Solvent acetonitrile—
Saturate acetonitrile with isooctane.
Solvent isooctane—
Saturate isooctane with acetonitrile.
4-Aminoantipyrine solution—
Dissolve about 200mg of 4-aminoantipyrine in a 1in 100solution of hydrochloric acid in methanol to make 50mLof solution,and mix.Prepare this solution on the day of use.
Standard preparation—
Dissolve a suitable quantity of USP Flumethasone Pivalate RS,accurately weighed,in Solvent acetonitrile,and dilute quantitatively and stepwise with Solvent acetonitrileto obtain a solution having a known concentration of about 40µg per mL.
Assay preparation—
Transfer an accurately weighed portion of Cream,equivalent to about 400µg of flumethasone pivalate,to a tared glass-stoppered,50-mLcentrifuge tube.Place the tube in a vacuum desiccator,and dry the specimen in vacuum over silica gel until about 70%loss in weight is obtained.
Procedure—
[NOTE—Perform the extractions in glass-stoppered,50-mLcentrifuge tubes with separation being effected by centrifugation,the portion to be retained being withdrawn into a hypodermic syringe fitted with a blunt-end,14-gauge,15-cm needle.]Add 10.0mLof Solvent acetonitrileto the Assay preparation,and transfer 10.0mLof the Standard preparationto a separate,glass-stoppered,50-mLcentrifuge tube.Add 25mLof Solvent isooctaneto each tube,shake by mechanical means until the cream is dispersed,and then shake both mixtures for 5minutes.Separate and withdraw each acetonitrile layer,and filter through cotton pledgets,previously saturated with Solvent acetonitrile,into separate 25-mLvolumetric flasks.Repeat the extraction,using a 10-mLportion of Solvent acetonitrilefor each tube.Separate,withdraw,and filter each acetonitrile layer through the same respective filter,and combine the extracts with the main extracts.Dilute each with Solvent acetonitrileto volume,and mix.Transfer 10.0mLof each solution to separate,glass-stoppered,20-mLtubes,and to a third tube transfer 10.0mLof Solvent acetonitrileto provide the blank.Evaporate the solvent on a water bath (about 75)with the aid of a stream of nitrogen.Add 5.0mLof 4-Aminoantipyrine solutionto each tube,insert the stopper,shake by mechanical means until the residue dissolves,and allow to stand for 1hour.Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 390nm,with a suitable spectrophotometer,against the blank.Calculate the quantity,in mg,of flumethasone pivalate (C27H36F2O6)in the portion of Cream taken by the formula:
)with the aid of a stream of nitrogen.Add 5.0mLof 4-Aminoantipyrine solutionto each tube,insert the stopper,shake by mechanical means until the residue dissolves,and allow to stand for 1hour.Concomitantly determine the absorbances of the solutions in 1-cm cells at the wavelength of maximum absorbance at about 390nm,with a suitable spectrophotometer,against the blank.Calculate the quantity,in mg,of flumethasone pivalate (C27H36F2O6)in the portion of Cream taken by the formula:
0.01C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Flumethasone Pivalate RSin the Standard preparation;and AUand ASare the absorbances of the solutions from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 835
Phone Number:1-301-816-8139