Neomycin Sulfate and Prednisolone Sodium Phosphate Ophthalmic Ointment
»Neomycin Sulfate and Prednisolone Sodium Phosphate Ophthalmic Ointment is a sterile ointment containing Neomycin Sulfate and Prednisolone Sodium Phosphate.It contains the equivalent of not less than 90.0percent and not more than 135.0percent of the labeled amount of neomycin,and the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amount of prednisolone phosphate (C21H29O8P).
NOTE—Where Neomycin Sulfate and Prednisolone Sodium Phosphate Ophthalmic Ointment is prescribed without reference to the quantity of neomycin or prednisolone phosphate contained therein,a product containing 3.5mg of neomycin and 2.5mg of prednisolone phosphate per g shall be dispensed.
Packaging and storage— Preserve in collapsible ophthalmic ointment tubes.
Identification—
A: It responds to the Identificationtest under Neomycin Sulfate Cream.
B: Shake a quantity of Ophthalmic Ointment,equivalent to about 40mg of prednisolone phosphate,with 25mLof sodium chloride solution (1in 20)and 25mLof methylene chloride,for 2minutes.Transfer the methylene chloride layer to a second separator containing 15mLof sodium chloride (1in 20).Shake for 1minute,and discard the methylene chloride layer.Repeat the operation with a second portion of 25mLof methylene chloride.Combine the aqueous phase from the second separator with the aqueous phase of the first separator.Add 10mLof Alkaline phosphatase solution,prepared as directed in the Assay for prednisolone phosphate,and add 50mLof methylene chloride.Insert the stopper,and allow to stand,with occasional gentle inversion (about once every 15minutes),for 2hours.Filter the methylene chloride layer through a dry paper,and evaporate 25mLof the filtrate to dryness:the residue so obtained responds to Identificationtest Aunder Prednisolone.
Sterility á71ñ: meets the requirements.
Minimum fill á755ñ: meets the requirements.
Water,Method Iá921ñ: not more than 1.0%,20mLof a mixture of toluene and methanol (7:3)being used in place of methanol in the titration vessel.
Metal particles— It meets the requirements of the test for Metal Particles in Ophthalmic Ointments á751ñ.
Assay for neomycin— Proceed as directed under Antibiotics—Microbial Assays á81ñ,using an accurately weighed portion of Ophthalmic Ointment shaken in a separator with about 50mLof ether,and extracted with four 20-mLportions of Buffer No.3.Combine the aqueous extracts,and dilute with Buffer No.3to an appropriate volume to obtain a stock solution.Dilute this stock solution quantitatively and stepwise with Buffer No.3to obtain a Test Dilutionhaving a concentration assumed to be equal to the median dose level of the Standard.
Assay for prednisolone phosphate—
pH9buffer with magnesium— Prepare as directed in the Assayunder Dexamethasone Sodium Phosphate.
Alkaline phosphatase solution— Prepare as directed in the Assayunder Dexamethasone Sodium Phosphate Injection.
Standard preparation— Prepare as directed for Standard Preparationunder Assay for Steroids á351ñ,using USP Prednisolone RS.
Assay preparation— Transfer an accurately weighed portion of Ophthalmic Ointment,equivalent to about 3mg of prednisolone phosphate,to a 125-mLseparator.Add 25mLof sodium chloride solution (1in 20)and 25mLof methylene chloride,and shake for not less than 2minutes to disperse the assay specimen.Transfer the methylene chloride layer to a second separator containing 15mLof sodium chloride solution (1in 20).Shake for 1minute,and discard the methylene chloride layer.Repeat the operation with a second portion of 25mLof methylene chloride.Transfer the aqueous phases from both separators to a 50-mLvolumetric flask,rinsing the first separator with the aqueous phase of the second separator.Rinse both separators with the same 5mLof sodium chloride solution (1in 20),and add the rinsing to the volumetric flask.Add sodium chloride solution (1in 20)to volume,and mix.
Pipet 5mLof the resulting solution into a 125-mLseparator,add 8.0mLof Alkaline phosphatase solution,mix,and allow to stand for 2hours.Extract the solution with two 25-mLportions of methylene chloride,filtering the extracts through methylene chloride-washed cotton into a small beaker.Evaporate the methylene chloride on a steam bath nearly to dryness,then evaporate with the aid of a current of air to dryness.Dissolve the residue in 25.0mLof alcohol.
Prepare a blank by evaporating 50mLof methylene chloride to dryness and dissolving the residue in 25mLof alcohol.
Procedure— Pipet 20mLeach of the Assay preparation,the Standard preparation,and the blank solution into separate glass-stoppered flasks,and proceed as directed for Procedureunder Assay for Steroids á351ñ,beginning with “add 2.0mLof a solution prepared by dissolving 50mg of blue tetrazolium.”Calculate the quantity,in mg,of prednisolone phosphate (C21H29O8P)in the portion of Ophthalmic Ointment taken by the formula:
0.25C(AU/AS)(440.43/360.45),
in which Cis the concentration,in µg per mL,of USP Prednisolone RSin the Standard preparation,AUand ASare the absorbances of the solutions from the Assay preparationand the Standard preparation,respectively,and 440.43and 360.45are the molecular weights of prednisolone phosphate and prednisolone,respectively.
Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1363
Phone Number:1-301-816-8335