Aluminum Zirconium Octachlorohydrate
AlyZr(OH)3y+4-xClx·nH2O
»Aluminum Zirconium Octachlorohydrate is a polymeric,loosely hydrated complex of basic aluminum zirconium chloride that encompasses a range of aluminum-to-zirconium atomic ratios between 6.0:1and 10.0:1,and a range of (aluminum plus zirconium)-to-chloride atomic ratios between 1.5:1and 0.9:1.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of anhydrous aluminum zirconium octachlorohydrate.
Packaging and storage— Preserve in well-closed containers.
Labeling— The label states the content of anhydrous aluminum zirconium octachlorohydrate.
Identification— Asolution (1in 10)responds to the test for Chloride á191ñ.
pHá791ñ: between 3.0and 5.0,in a solution [15in 100(w/w)].
Heavy metals,Method Iá231ñ— Proceed as directed in the chapter,except to use the following modifications.
Test Preparation— Prepare as directed in the chapter.If the solution is not clear after dilution to 40mL,heat for several minutes between 60and 80,and cool to room temperature.If the solution remains cloudy,repeat from the beginning with the following modification:add 3mLof hydrochloric acid prior to adjustment of the pHwith 6Nammonium hydroxide.
Monitor Preparation— Prepare as directed in the chapter,using the same modifications described for Test Preparationif necessary.
Procedure— To each of the three tubes containing the Standard Preparation,the Test Preparation,and the Monitor Preparation,add 2mLof pH3.5Acetate Buffer,and heat gently to between 60and 80.To the Standard Preparationadd 6drops of sodium sulfide TS.To the Test Preparationand the Monitor Preparationadd 12drops of sodium sulfide TS.Cool to room temperature,and dilute the contents of each tube with water to 50mL.Gently mix each tube by inverting twice.Allow to stand for 5minutes,and view downward over a white surface.The color of the solution from the Test Preparationis not darker than that of the solution from the Standard Preparation,and the color of the solution from the Monitor Preparationis the same as or darker than the color of the solution from the Standard Preparation.If the color of the solution from the Monitor Preparationis lighter than the color of the solution from the Standard Preparation,repeat the procedure with the following modification:after the heating step,to the Monitor Preparationand the Test Preparationadd 1.0mL,instead of 12drops,of sodium sulfide TS.Not more than 20µg per g is found.
Limit of iron—
Standard preparation— Transfer 2.0mLof Standard Iron Solution,prepared as directed under Iron á241ñ,to a 50-mLbeaker.
Test preparation— Transfer 2.7g of Aluminum Zirconium Octachlorohydrate to a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof this solution to a 50-mLbeaker.
Procedure— To each of the beakers containing the Standard preparationand the Test preparationadd 5mLof 6Nnitric acid,cover with a watch glass,and boil on a hot plate for 3to 5minutes.Allow to cool,add 5mLof Ammonium Thiocyanate Solution,prepared as directed under Iron á241ñ,transfer to separate 50-mLcolor comparison tubes,dilute with water to volume,and mix:the color of the solution from the Test preparationis not darker than that of the solution from the Standard preparation(150µg per g).
Content of aluminum— Transfer about 0.15g of Aluminum Zirconium Octachlorohydrate,accurately weighed,to a 150-mLbeaker,and add 5mLof water and 15mLof hydrochloric acid.Heat this solution to boiling,and continue boiling for 5minutes.Add 40mLof water and 15.0mLof 0.1Medetate disodium VS.Heat the solution to boiling,and continue boiling for 5minutes.Allow the solution to cool,add 10to 15mLof acetic acid–ammonium acetate buffer TS,and adjust with ammonium hydroxide to a pHof 4.5±0.1.Add 20mLof alcohol,and adjust with ammonium hydroxide to a pHof 4.6±0.1.Add 5to 10drops of dithizone TS,and titrate with 0.1Mzinc sulfate VSuntil the first permanent purple-pink color appears.Perform a blank determination,and make any necessary correction.Calculate the percentage of aluminum (Al)in the Aluminum Zirconium Octachlorohydrate by the formula:
2.698[15.0Me-(zMz+Ze)]/W,
in whichMeis the molarity of the edetate disodium VS;zis the volume,in mL,of zinc sulfate VSconsumed;Mzis the molarity of the zinc sulfate VS;Wis the quantity,in g,of Aluminum Zirconium Octachlorohydrate taken;Zeis the equivalent volume,in mL,of edetate disodium VSconsumed by the zirconium moiety,calculated as follows:
(Zr/Me)(W/92.97),
in which Zris the percentage of zirconium as determined in the test for Content of zirconium,92.97is the atomic weight of zirconium corrected for 2%hafnium content,and the other terms are as defined above.Use the result obtained to calculate the Aluminum/zirconium atomic ratioand the (Aluminum plus zirconium)/chloride atomic ratio.
Content of zirconium— Transfer about 250mg of Aluminum Zirconium Octachlorohydrate,accurately weighed,to a 150-mLbeaker,and add 5mLof water and 15mLof hydrochloric acid.Heat this solution to boiling,and continue boiling for 6to 8minutes.Add 30to 40mLof water and 5mLof hydrochloric acid,and heat to boiling.Add 1drop of xylenol orange TS,and,while still hot,titrate with 0.1Medetate disodium VSuntil the color of the solution changes from pink to yellow.Perform a blank determination,and make any necessary correction.Each mLof 0.1Medetate disodium is equivalent to 9.297mg of zirconium (Zr).Use the result obtained to calculate the Aluminum/zirconium atomic ratioand the (Aluminum plus zirconium)/chloride atomic ratio.
Aluminum/zirconium atomic ratio— Divide the percentage of aluminum found in the test for Content of aluminumby the percentage of zirconium found in the test for Content of zirconium,and multiply by 92.97/26.98,in which 92.97is the atomic weight of zirconium corrected for 2%hafnium content,and 26.98is the atomic weight of aluminum:the ratio is between 6.0:1and 10.0:1.
Content of chloride— Transfer about 250mg of Aluminum Zirconium Octachlorohydrate,accurately weighed,to a 250-mLbeaker,add 100to 120mLof water and 20mLof diluted nitric acid,and swirl to dissolve.Titrate with 0.05Nsilver nitrate VSusing a calomel electrode and a silver billet electrode system,determining the endpoint potentiometrically.Each mLof 0.05Nsilver nitrate is equivalent to 1.773mg of chloride (Cl).Use the result obtained to calculate the (Aluminum plus zirconium)/chloride atomic ratio.
(Aluminum plus zirconium)/chloride atomic ratio— Calculate the (aluminum plus zirconium)/chloride atomic ratio by the formula:
[(Al/26.98)+(Zr/92.97)]/(Cl/35.453),
in which Al,Zr,and Clare the percentages of aluminum,zirconium,and chloride as determined in the tests for Content of aluminum,Content of zirconium,and Content of chloride,respectively;26.98is the atomic weight of aluminum;92.97is the atomic weight of zirconium corrected for 2%hafnium content;and 35.453is the atomic weight of chlorine:the ratio is between 1.5:1and 0.9:1.
Assay— Calculate the percentage of anhydrous aluminum zirconium octachlorohydrate in the Aluminum Zirconium Octachlorohydrate by the formula:
Al({26.98y+92.97+17.01[3y+4-(y+1)/z]+35.453(y+1)/z}/26.98y),
in which Alis the percentage of aluminum found in the test for Content of aluminum,yis the aluminum/zirconium atomic ratio found in the test for Aluminum/zirconium atomic ratio,zis the (aluminum plus zirconium)/chloride atomic ratio found in the test for (Aluminum plus zirconium)/chloride atomic ratio,26.98is the atomic weight of aluminum,92.97is the atomic weight of zirconium corrected for 2%hafnium content,17.01is the molecular weight of the hydroxide anion (OH),and 35.453is the atomic weight of chlorine (Cl).
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 97
Pharmacopeial Forum:Volume No.27(4)Page 2691
Phone Number:1-301-816-8389