Alumina,Magnesia,and Calcium Carbonate Oral Suspension
»Alumina,Magnesia,and Calcium Carbonate Oral Suspension contains not less than 90.0percent and not more than 110.0percent of the labeled amounts of aluminum hydroxide [Al(OH)3],magnesium hydroxide [Mg(OH)2],and calcium carbonate (CaCO3).
Packaging and storage— Preserve in tight containers,and avoid freezing.
Labeling— Oral Suspension may be labeled to state the aluminum hydroxide content in terms of the equivalent amount of dried aluminum hydroxide gel,on the basis that each mg of dried gel is equivalent to 0.765mg of Al(OH)3.
Identification—
A: To 5g of Oral Suspension add 25mLof 2Nsulfuric acid,stir,and allow to stand for 5minutes.Add 25mLof alcohol,stir,and place in an ice bath for 30minutes.Filter while cold,retaining the filtrate forIdentificationtestB.Wash the precipitate with 50mLof 0.75Nsulfuric acid,and discard the washings:the precipitate so obtained,dissolved in 3Nhydrochloric acid and filtered,responds to the tests forCalcium á191ñ.
B: To the filtrate obtained inIdentificationtestAadd 5drops of methyl red TS,and heat to boiling.Add 6Nammonium hydroxide until the color of the solution changes to deep yellow,continue boiling for 2minutes,and filter through hardened filter paper.(Retain the filtrate forIdentificationtestC.)Wash the precipitate with 350mLof a hot ammonium chloride solution (1in 50),discarding the washings:the precipitate so obtained,dissolved in 3Nhydrochloric acid,responds to the tests forAluminum á191ñ.
C: The filtrate obtained inIdentificationtestBresponds to the tests forMagnesium á191ñ.
Microbial limits á61ñ— Its total aerobic microbial count does not exceed 100cfu per mL,and it meets the requirements of the test for absence ofEscherichia coli.
Acid-neutralizing capacity á301ñ— Not less than 5mEq of acid is consumed by the minimum single dose recommended in the labeling,and not less than the number of mEq calculated by the formula:
0.55(0.0385A)+0.8(0.0343M)+0.9(0.02C),
in which 0.0385,0.0343,and 0.02are the theoretical acid-neutralizing capacities,in mEq,of Al(OH)3,Mg(OH)2,and CaCO3,respectively,and A,M,andCare the respective quantities,in mg,of Al(OH)3,Mg(OH)2,and CaCO3in the specimen tested,based on the labeled quantities.
pHá791ñ: between 7.5and 8.5.
Chloride á221ñ— Dissolve 5.0g in 3mLof nitric acid,add water to make 100mL,and filter:a 10.0-mLportion of the filtrate shows no more chloride than corresponds to 1.0mLof 0.020Nhydrochloric acid (0.14%).
Sulfate á221ñ— Dissolve 5.0g in 7mLof 3Nhydrochloric acid,with gentle heating.Cool,add water to make 250mL,mix,and filter:a 20.0-mLportion of the filtrate shows no more sulfate than corresponds to 0.40mLof 0.020Nsulfuric acid (0.1%).
Other requirements— It meets the requirements of the tests forArsenic andHeavy metalsunderAluminum Hydroxide Gel.
Assay for aluminum hydroxide—
Edetate disodium titrant— Prepare and standardize as directed in theAssayunderAmmonium Alum.
Assay preparation— Transfer an amount of Oral Suspension,previously shaken in its original container,equivalent to about 600mg of aluminum hydroxide,to a tared beaker,and weigh accurately.Add 20mLof water,stir,and slowly add 40mLof 3Nhydrochloric acid.Heat gently,if necessary,to aid solution,cool,and transfer to a 200-mLvolumetric flask.Wash the beaker with water,adding the washings to the flask,add water to volume,and mix.
Procedure— Pipet 10mLof theAssay preparationinto a 250-mLbeaker,add 20mLof water,then add,in the order named and with continuous stirring,25.0mLof 0.05MEdetate disodium titrant and 20mLof acetic acid–ammonium acetate buffer TS,and heat the solution near the boiling temperature for 5minutes.Cool,add 50mLof alcohol and 2mLof dithizone TS,and mix.Titrate with 0.05Mzinc sulfate VSuntil the color changes from green-violet to rose-pink.Perform a blank determination,substituting 10mLof water for theAssay preparation,and make any necessary correction.Each mLof 0.05MEdetate disodium titrant consumed is equivalent to 3.900mg of Al(OH)3.
Assay for magnesium hydroxide—
Assay preparation— Prepare as directed in theAssay for aluminum hydroxide.
Procedure— Pipet a volume ofAssay preparation,equivalent to about 40mg of magnesium hydroxide,into a 400-mLbeaker,add 200mLof water and 20mLof trolamine,and mix.Add 50mLof ammonia–ammonium chloride buffer TSand 2drops of eriochrome black indicator solution (prepared by dissolving 200mg of eriochrome black Tin a mixture of 15mLof trolamine and 5mLof dehydrated alcohol,and mixing).Cool the solution to between 3and 4by immersing the beaker in an ice bath,and titrate with 0.05Medetate disodium VSuntil the color changes to pure blue.Perform a blank determination,substituting 10mLof water for theAssay preparation,and make any necessary correction.From the volume of 0.05Medetate disodium consumed,subtract the volume of 0.05Medetate disodium consumed in theAssay for calcium carbonate.Each mLof 0.05Medetate disodium is equivalent to 2.916mg of Mg(OH)2.
Assay for calcium carbonate—
Assay preparation— Prepare as directed in theAssay for aluminum hydroxide.
Procedure— Pipet a volume of theAssay preparation,equivalent to about 50mg of calcium carbonate,into a 400-mLbeaker,and add 200mLof water,5mLof sodium hydroxide solution (1in 2),and 250mg of hydroxy naphthol blue.Stir with a magnetic stirrer,and titrate immediately with 0.05Medetate disodium VSuntil the solution is distinctly blue.Each mLof 0.05Medetate disodium is equivalent to 5.004mg of calcium carbonate (CaCO3).
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 78
Pharmacopeial Forum:Volume No.27(6)Page 3241
Phone Number:1-301-816-8251