Alumina,Magnesia,and Simethicone Oral Suspension
»Alumina,Magnesia,and Simethicone Oral Suspension contains the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amounts of aluminum hydroxide [Al(OH)3]and magnesium hydroxide [Mg(OH)2],and an amount of polydimethylsiloxane [-(CH3)2SiO-]nthat is not less than 85.0percent and not more than 115.0percent of the labeled amount of simethicone.
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.Label it to state the sodium content if it is greater than 1mg per mL.
Identification—
A:
Infrared Absorption á197Sñ—
Cell:
0.5mm.
Solution:
prepared as directed in the Assay for polydimethylsiloxane.
B:
To a solution of 5g in 10mLof 3Nhydrochloric acid add 5drops of methyl red TS,heat to boiling,add 6Nammonium hydroxide until the color of the solution just changes to deep yellow,then continue boiling for 2minutes,and filter:the filtrate so obtained responds to the tests for Magnesium á191ñ.
C:
Wash the precipitate obtained in Identificationtest Bwith hot ammonium chloride solution (1in 50),and dissolve the precipitate in hydrochloric acid.Divide this solution into two portions:the dropwise addition of 6Nammonium hydroxide to one portion yields a gelatinous white precipitate,which does not dissolve in an excess of 6Nammonium hydroxide.The dropwise addition of 1Nsodium hydroxide to the other portion yields a gelatinous white precipitate,which dissolves in an excess of 1Nsodium hydroxide,leaving some turbidity.
Microbial limits á61ñ—
Its total aerobic microbial count does not exceed 100cfu per mL,and it meets the requirements of the test for absence of Escherichia coli.
Acid-neutralizing capacity á301ñ—
The acid consumed by the minimum single dose recommended in the labeling is not less than 5mEq,and not less than the number of mEq calculated by the formula:
0.55(0.0385A)+0.8(0.0343M),
in which 0.0385and 0.0343are the theoretical acid-neutralizing capacities,in mEq,of Al(OH)3and Mg(OH)2,respectively,and Aand Mare the quantities,in mg,of Al(OH)3and Mg(OH)2in the specimen tested,based on the labeled quantities.
Defoaming activity—
Foaming solution—
Dissolve 500µg of FD&C Blue No.1and 1g of octoxynol 9in 100mLof 0.1Nhydrochloric acid.
Procedure—
[NOTE—For each test,employ a clean,unused,250-mLglass jar.]Transfer a volume of Oral Suspension,equivalent to 20mg of simethicone,to a clean,unused,cylindrical 250-mLglass jar,fitted with a 50-mm cap,containing 100mLof Foaming solutionthat has been warmed to 37
.Proceed as directed for Procedurein the test for Defoaming activityunder Simethicone,beginning with “Cap the jar.”The defoaming activity time does not exceed 45seconds.
.Proceed as directed for Procedurein the test for Defoaming activityunder Simethicone,beginning with “Cap the jar.”The defoaming activity time does not exceed 45seconds.
pHá791ñ:
between 7.0and 8.6.
Sodium content—
Potassium chloride solution—
Prepare a solution of potassium chloride in water containing 38mg per mL.
Sodium chloride stock solution—
Dissolve a suitable quantity of sodium chloride,previously dried at 105for 2hours and accurately weighed,in water,and dilute quantitatively and stepwise with water to obtain a solution containing 25.42µg per mL(10µg of sodium per mL).
for 2hours and accurately weighed,in water,and dilute quantitatively and stepwise with water to obtain a solution containing 25.42µg per mL(10µg of sodium per mL).
Standard preparations—
On the day of use,transfer 4.0mLof 1Nhydrochloric acid and 10.0mLof Potassium chloride solutionto each of two 100-mLvolumetric flasks.To the respective flasks add 5.0mLand 10.0mLof Sodium chloride stock solution.Dilute with water to volume,and mix.These solutions contain about 0.5µg and 1.0µg of sodium per mL,respectively.
Test preparation—
Transfer 5.0mLof Oral Suspension,previously well-shaken in its original container,to a 100-mLvolumetric flask,add 50mLof 1Nhydrochloric acid,boil for 15minutes,cool to room temperature,dilute with water to volume,and mix.Filter,discarding the first few mLof the filtrate.Transfer 5.0mLof the filtrate to a 100-mLvolumetric flask containing 10.0mLof Potassium chloride solution,dilute with water to volume,and mix.
Procedure—
Concomitantly determine the absorbances of the Standard preparationsand the Test preparationat the sodium emission line at 589.0nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering á851ñ)equipped with a sodium hollow-cathode lamp and an air–acetylene flame,using as a blank a solution prepared by pipeting 4mLof 1Nhydrochloric acid and 10.0mLof Potassium chloride solutioninto a 100-mLvolumetric flask,diluting with water to volume,and mixing.Plot the absorbances of the Standard preparationsversus concentrations,in µg per mL,of sodium and draw a straight line between the plotted points.From the graph so obtained,determine the concentration,C,in µg per mL,of sodium in the Test preparation.Calculate the quantity,in mg,of sodium in each mLof Oral Suspension taken by the formula:
0.4C.
Assay for aluminum hydroxide—
Assay preparation—
Transfer an accurately measured volume of Oral Suspension,previously well-shaken in its original container,equivalent to about 800mg of aluminum hydroxide,to a suitable beaker.Add 20mLof water,stir,and slowly add 10mLof hydrochloric acid.Heat gently,if necessary,to aid solution,cool,and filter into a 200-mLvolumetric flask.Wash the filter with water into the flask,add water to volume,and mix.
Procedure—
Pipet 10mLof the Assay preparationinto a 250-mLbeaker,add 20mLof water,then add,in the order named and with continuous stirring,25.0mLof Edetate disodium titrantand 20mLof acetic acid-ammonium acetate buffer TS,and heat 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 the Assay preparation,and making any necessary correction.Each mLof 0.05M Edetate disodium titrantconsumed is equivalent to 3.900mg of Al(OH)3.
Assay for magnesium hydroxide—
Assay preparation—
Prepare as directed in the Assay for aluminum hydroxide.
Procedure—
Pipet a volume of the Assay preparation,equivalent to about 40mg of magnesium hydroxide,into a 400-mLbeaker,add 200mLof water and 20mLof triethanolamine,and stir.Add 10mLof ammonia-ammonium chloride buffer TSand 3drops of an eriochrome black indicator solution prepared by dissolving 200mg of eriochrome black Tin a mixture of 15mLof triethanolamine and 5mLof dehydrated alcohol,and mix.Cool the solution to between 3and 4by immersion of the beaker in an ice bath,then remove,and titrate with 0.05Medetate disodium VSto a blue endpoint.Perform a blank determination,substituting water for the Assay preparation,and make any necessary correction.Each mLof 0.05Medetate disodium consumed is equivalent to 2.916mg of Mg(OH)2.
and 4by immersion of the beaker in an ice bath,then remove,and titrate with 0.05Medetate disodium VSto a blue endpoint.Perform a blank determination,substituting water for the Assay preparation,and make any necessary correction.Each mLof 0.05Medetate disodium consumed is equivalent to 2.916mg of Mg(OH)2.
Assay for polydimethylsiloxane—
Transfer an accurately measured volume of Oral Suspension,equivalent to about 50mg of simethicone,to a suitable round,narrow-mouth,screw-capped,120-mLbottle,add 40mLof 0.1Nsodium hydroxide,and swirl to disperse.Add 25.0mLof toluene,close the bottle securely with a cap having an inert liner,and shake for 15minutes,accurately timed,on a reciprocating shaker (e.g.,about 200oscillations per minute and a stroke of 38±2mm).Transfer the mixture to a 125-mLseparator.Remove about 5mLof the upper,organic layer to a screw-capped,15-mLtest tube containing 0.5g of anhydrous sodium sulfate.Close the tube with a screw-cap having an inert liner,agitate vigorously,and centrifuge the mixture until a clear supernatant (Assay preparation)is obtained.Prepare a Standard preparationsimilarly,except to dissolve about 50mg of USP Polydimethylsiloxane RS,accurately weighed,in 25.0mLof toluene,add 40mLof 0.1Nsodium hydroxide,and add a volume of water equal to that of the specimen of Oral Suspension taken.Prepare a blank by mixing 10mLof toluene with 0.5g of anhydrous sodium sulfate and centrifuging to obtain a clear supernatant.Concomitantly determine the absorbances of the solutions in 0.5-mm cells at the wavelength of maximum absorbance at about 7.9µm,with a suitable IRspectrophotometer,using the blank to set the instrument.Calculate the quantity,in mg,of [-(CH3)2SiO-]nin each mLof the Oral Suspension taken by the formula:
(W/V)(AU/AS),
in which Wis the weight,in mg,of USP Polydimethylsiloxane RSused in preparing the Standard preparation;Vis the volume,in mL,of Oral Suspension taken;and AUand ASare the absorbances of the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 81
Phone Number:1-301-816-8251