Brinzolamide Ophthalmic Suspension
»Brinzolamide Ophthalmic Suspension is a sterile,aqueous suspension of Brinzolamide containing a suitable antimicrobial preservative.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of brinzolamide (C12H21N3O5S3).
Packaging and storage— Preserve in tight containers.Store at a temperature between 4and 30.
Identification— The retention time of the major peak in the chromatogram of theAssay preparationcorresponds to that in the chromatogram of theStandard preparation,as obtained in the Assay.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined.
pHá791ñ: between 6.5and 8.5.
Related compounds—
TEST1—
Mobile phase,System suitability solution,andChromatographic system— Proceed as directed in Test 1for Related compoundsunder Brinzolamide.
Test solution— Transfer an accurately weighed volume of Ophthalmic Suspension,equivalent to about 10mg of brinzolamide,to a 25-mLvolumetric flask,dilute with alcohol to volume,and mix.
Procedure— Proceed as directed in Test 1for Related compoundsunder Brinzolamide:not more than 1.5%of brinzolamide related compound Ais found.
TEST2—
Buffer solutionandMobile phase— Proceed as directed in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Brinzolamide Related Compound B RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,to obtain a solution having a known concentration of about 2.5µg per mL.
Test solution— Use the Assay preparation.
Chromatographic system— Proceed as directed in the Assay,and chromatograph the System suitability preparation,prepared as directed in the Assay,and the Standard solution,instead of the Standard preparation.
Procedure— Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the areas for all the peaks.Calculate the quantity,in mg,of each impurity in the portion of Ophthalmic Suspension taken by the formula:
(356.46/445.49)50C(ri/rS),
in which 356.46and 445.49are the molecular weights of des-ethyl brinzolamide and des-ethyl brinzolamide oxalate,respectively;Cis the concentration,in mg per mL,of USP Brinzolamide Related Compound B RSin the Standard solution;riis peak response for each impurity obtained from the Test solution;and rSis the peak response for USP Brinzolamide Related Compound B RSobtained from the Standard solution:not more than 0.5%of any individual impurity is found;and not more than 2.0%of total impurities is found.
Assay—
Buffer solution— Dissolve 11.75g of ammonium acetate in about 1000mLof water.Adjust with acetic acid to a pHof 5.2.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solutionand methanol (65:35).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Brinzolamide RSin Mobile phaseto obtain a solution having a known concentration of about 0.2mg per mL.
System suitability preparation— Dissolve an accurately weighed quantity of USP Brinzolamide Related Compound B RSin Standard preparationto obtain a solution having a known concentration of about 0.06mg per mL.
Assay preparation— Transfer an accurately measured volume of Ophthalmic Suspension,equivalent to about 10mg of brinzolamide,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 1.0mLper minute.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the relative retention times are between 0.48and 0.61for brinzolamide related compound Band 1.0for brinzolamide;the resolution,R,between brinzolamide and brinzolamide related compound Bis not less than 4.5;the column efficiency is not less than 2500theoretical plates;and the tailing factor is not more than 2.0.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of brinzolamide (C12H21N3O5S3)in the portion of Ophthalmic Suspension taken by the formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Brinzolamide RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 282
Pharmacopeial Forum:Volume No.28(6)Page 1774
Phone Number:1-301-816-8389