Clocortolone Pivalate Cream
»Clocortolone Pivalate Cream contains not less than 90.0percent and not more than 110.0percent of C27H36ClFO5in a suitable cream base.It may contain suitable preservatives.
Packaging and storage— Preserve in collapsible tubes or in tight,light-resistant containers.
Identification— Place a portion of Cream,equivalent to about 1mg of clocortolone pivalate,in a suitable separator.Add 5mLof water,and extract with 10mLof chloroform.Evaporate the chloroform layer to dryness,and dissolve the residue in 2mLof methanol.Apply 20µLof this test solution and 20µLof a Standard solution of USP Clocortolone Pivalate RSin chloroform containing about 0.5mg per mLabout 1.5cm from the bottom of 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 a solvent system consisting of cyclohexane and ethyl acetate (2:1)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.Locate the spots on the plate by viewing under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Minimum fill á755ñ: meets the requirements.
pHá791ñ: between 5.0and 7.0,in a 1in 10aqueous dispersion.
Particle size determination— Place a small portion of Cream on a microscope slide,apply a cover slide,press slightly,and examine under 40×objective magnification using a suitable microscope equipped with polarized light.Scan the complete slide preparation,and record the size of the largest crystal found in reference to a calibrated grid:no particle in the Cream is greater than 50microns when measured in the longitudinal axis.
Assay—
Standard preparation— Dissolve an accurately weighed quantity of USP Clocortolone Pivalate RSin methanol to obtain a solution having a known concentration of about 0.06mg per mL.
Assay preparation— Using a plastic syringe equipped with a suitable cannula,transfer an accurately weighed quantity of Cream,equivalent to about 3mg of clocortolone pivalate,to a 50-mLvolumetric flask.Add about 25mLof methanol,and warm the flask in a 60water bath for about 10minutes,with occasional swirling,to disperse the Cream.Cool to room temperature,dilute with methanol to volume,and mix.Allow any insoluble material to settle.
Procedure— Transfer 10.0mLof the Standard preparationto a 25-mLvolumetric flask.Transfer 10.0-mLportions of the Assay preparationinto two separate 25-mLvolumetric flasks labeled Assay preparationand Assay blank,respectively.Evaporate the contents of the three flasks with the aid of a stream of air or nitrogen to dryness.Transfer 20.0mLof a solution containing 250mg of isoniazid and 0.3mLof hydrochloric acid in 500mLof methanol to the flasks containing the Standard preparation,the Assay preparation,and a fourth 25-mLvolumetric flask labeled Reagent blank.Pipet 20mLof acidified methanol solution (0.3mLof hydrochloric acid diluted with methanol to 500mL)into the flask labeled Assay blank.Insert the stoppers securely in the flasks,and place in a water bath at 60for 2.5hours,occasionally swirling the contents of each flask.Cool the flasks to room temperature,dilute with the acidified methanol solution to volume,and mix.Centrifuge the Assay preparationat high speed for 10minutes.Concomitantly determine the absorbances of the Standard preparation,the Assay preparation,the Assay blank,and the Reagent blankagainst acidified methanol solution as the solvent blank in 1-cm cells at the wavelength of maximum absorbance at about 390nm,with a suitable spectrophotometer.Calculate the quantity,in mg,of C27H36ClFO5in the portion of Cream taken by formula:
50C(AU/AS),
in which Cis the concentration,in mg per mL,of USP Clocortolone Pivalate RSin the Standard preparation,AUis the absorbance of the Assay preparation,corrected for the Assay blankand the Reagent blank,and ASis the absorbance of the Standard preparationcorrected for the Reagent blank.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 505
Phone Number:1-301-816-8139