Magaldrate and Simethicone Oral Suspension
»Magaldrate and Simethicone Oral Suspension contains not less than 90.0percent and not more than 110.0percent of the labeled amount of magaldrate [Al5Mg10(OH)31(SO4)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 keep from freezing.
Identification—
A: Dissolve an amount of Oral Suspension,equivalent to about 800mg of magaldrate,in 20mLof 3Nhydrochloric acid,dilute with water to about 50mL,add 3drops of methyl red TS,and proceed as directed in Identificationtest Aunder Magaldrate,beginning with “and heat to boiling.”
B: Wash the precipitate obtained in Identificationtest Awith 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.
C: Transfer an amount of Oral Suspension,equivalent to about 1g of magaldrate,to a 100-mLcentrifuge tube.Add about 60mLof water,insert the cap,and shake for 3minutes.Centrifuge the suspension,and discard the supernatant.Repeat the washing of the residue with three 60-mLportions of water.Transfer the residue to a 250-mLbeaker,and heat on a steam bath to dryness:the X-ray diffraction pattern (see X-ray Diffraction á941ñ),in the d-spacings region below 2.57angstrom units,of the residue so obtained conforms to that of USP Magaldrate RS.
D: The IRabsorption spectrum,in the 7-to 15-µm region,determined in a 0.1-mm cell,of the Assay preparationprepared as directed in the Assay for polydimethylsiloxaneexhibits maxima only at the same wavelengths as that of the Standard preparationprepared as directed in the Assay for polydimethylsiloxane.
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:
0.8(0.0282M),
in which 0.0282is the theoretical acid-neutralizing capacity,in mEq per mg,of magaldrate;andMis the quantity,in mg,of the labeled amount of magaldrate.
Defoaming activity—
Foaming solution— Dissolve 5mg of FD&C Blue No.1and 10g of polyoxyethylene (23)lauryl ether in 1000mLof water.Warm to 37before use.
Procedure— [NOTE—For each test use a clean 250-mLcylindrical jar (50-mm internal diameter ×110-mm internal height)with a 50-mm opening fitted with a tight cap with an inert liner.]Transfer a volume of well-mixed Oral Suspension,equivalent to 20mg of simethicone,to a 250-mLcylindrical jar containing 50mLof 0.6Nhydrochloric acid that has been warmed to 37.Cap the jar,and clamp it in an upright position on a wrist-action shaker.Employing a radius of 13.3±0.4cm (measured from the center of shaft to center of bottle),shake for 30seconds through an arc of 10degrees at a frequency of 300±30strokes per minute.Uncap the jar,add 50mLof Foaming solution,recap the jar,and shake for 10seconds using the conditions specified above.Record the time required for the foam to collapse.The time,in seconds,for foam collapse is determined at the instant the first portion of foam-free liquid surface appears,measured from the end of the shaking period.The defoaming activity time does not exceed 45seconds.
System suitability tests— [NOTE—For each of the following tests use a separate clean 250-mLcylindrical jar having the dimensions specified for Procedure.]Transfer 50mLof Foaming solutionto a 250-mLcylindrical jar containing 50mLof 0.6Nhydrochloric acid that has been warmed to 37.Cap the jar,and shake it for 10seconds using the conditions specified for Procedure:the foam layer remains intact for not less than 5minutes.Transfer 0.15mLof simethicone and 50mLof Foaming solutionto a second 250-mLcylindrical jar containing 50mLof 0.6Nhydrochloric acid that has been warmed to 37.Cap the jar,and shake it for 10seconds using the conditions specified for Procedure:the time required for the foam to collapse does not exceed 45seconds.
Magnesium hydroxide content—
Test preparation— Transfer an accurately measured quantity of Oral Suspension,equivalent to about 1g of magaldrate,to a 100-mLvolumetric flask,add 30mLof dilute hydrochloric acid (1in 10),shake to dissolve,dilute with water to volume,and mix.
Procedure— Transfer 10.0mLof Test preparationto a 400-mLbeaker,and proceed as directed in the test for Magnesium hydroxide contentunder Magaldrate,beginning with “and dilute with water to about 200mL.”Not less than 492mg and not more than 666mg of magnesium hydroxide [Mg(OH)2]per g of the labeled amount of magaldrate is found.
Aluminum hydroxide content—
Edetate disodium titrant— Prepare and standardize as directed in the Assayunder Ammonium Alum.
Test preparation— Prepare as directed in the test for Magnesium hydroxide content.
Procedure— Transfer 10.0mLof Test preparationand 20mLof water to a 250-mLbeaker,and proceed as directed for Procedurein the test for Aluminum hydroxide contentunder Magaldrate,beginning with “Add,with stirring,25.0mLof Edetate disodium titrant.”Not less than 321mg and not more than 459mg of aluminum hydroxide [Al(OH)3]per g of the labeled amount of magaldrate is found.
Other requirements— Evaporate a volume of Oral Suspension,equivalent to about 5g of magaldrate,on a steam bath to dryness:the residue so obtained meets the requirements of the tests for Arsenicand Heavy metalsunder Magaldrate.
Assay for magaldrate— Transfer an accurately measured quantity of Oral Suspension,equivalent to about 3g of magaldrate,to a beaker.Add 100.0mLof 1Nhydrochloric acid VS,and mix,using a magnetic stirrer to achieve dissolution.Titrate the excess acid with 1Nsodium hydroxide VSto a pHof 3.0,determined potentiometrically.Perform a blank determination (see Residual Titrationsunder Titrimetry á541ñ).Each mLof 1Nhydrochloric acid is equivalent to 35.40mg of magaldrate [Al5Mg10(OH)31(SO4)2].
Assay for polydimethylsiloxane— Transfer an accurately measured quantity of Oral Suspension,equivalent to about 250mg of simethicone,to a 200-mLcentrifuge bottle.Add an equal volume of hydrochloric acid,swirl to dissolve the Oral Suspension,add 25.0mLof hexanes,and immediately close the bottle securely with a cap having an inert liner.Shake the bottle for 30minutes,and centrifuge the mixture until a clear supernatant layer is obtained (Assay preparation).Prepare a Standard preparationof USP Polydimethylsiloxane RSin hexanes having a known concentration of about 10mg per mL.Concomitantly determine the absorbances of the Assay preparationand the Standard preparationin 0.1-mm cells at the wavelength of maximum absorbance at about 7.9µm and at the wavelengths of minimum absorbance at about 7.5µm and 8.3µm,with a suitable IRspectrophotometer,using hexanes as the blank.Draw a linear baseline between the two minima,and determine the absorbances for the Standard preparationand the Assay preparationwith respect to the baseline,making any necessary correction for the blank.Calculate the quantity,in mg,of [–(CH3)2SiO–]nin the portion of Oral Suspension taken by the formula:
25C(AU/AS),
in which Cis the concentration,in mg per mL,of USP Polydimethylsiloxane RSin the Standard preparation;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 1164
Phone Number:1-301-816-8251