»Simethicone is a mixture of fully methylated linear siloxane polymers containing repeating units of the formula [-(CH3)2SiO-]n,stabilized with trimethylsiloxy end-blocking units of the formula [(CH3)3SiO-],and silicon dioxide.It contains not less than 90.5percent and not more than 99.0percent of polydimethylsiloxane ([-(CH3)2SiO-]n),and not less than 4.0percent and not more than 7.0percent of silicon dioxide.
Packaging and storage Preserve in tight containers.
Identification, Infrared Absorption á197Sñ
Test solution Prepare as directed forAssay preparation in theAssay.
Standard solution Prepare as directed forStandard preparation in theAssay.
Cell size: 0.5mm.
Foaming solution Dissolve 1g of octoxynol 9in 100mLof water.
Test preparation Transfer 200mg of Simethicone to a 60-mLbottle,add 50mLof tertiary butyl alcohol,cap the bottle,and shake vigorously.[NOTEWarm slightly,if necessary,to effect solution.]
Procedure [NOTEFor each test,employ a clean,unused,250-mLglass jar.]Add,dropwise,500µLof theTest preparation to a clean,unused,cylindrical 250-mLglass jar,fitted with a 50-mm cap,containing 100mLof theFoaming solution.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 center of shaft to center of bottle),shake for 10seconds through an arc of 10degrees at a frequency of 300±30strokes per minute.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 15seconds.
Loss on heating Heat about 15g,accurately weighed,in an open,tared vessel having a diameter of 5.5±0.5cm and a wall height of 2.5±1.0cm at 200in a circulating air oven for 4hours,and allow to come to room temperature in a desiccator before weighing:it loses not more than 18.0%of its weight.
Heavy metals Mix 1.0g of Simethicone with 10mLof chloroform,and dilute with the same solvent to 20mL.Add 1.0mLof a freshly prepared 0.002%solution of dithizone in chloroform,0.5mLof water,and 0.5mLof a mixture of 1volume of ammonia TSand 9volumes of a 0.2%solution of hydroxylamine hydrochloride.Concomitantly prepare a Standard solution as follows:to 20mLof chloroform add 1.0mLof a freshly prepared 0.002%solution of dithizone in chloroform,0.5mLofStandard Lead Solution (seeHeavy Metals á231ñ)(containing 10µg of lead per mL)and 0.5mLof a mixture of 1volume of ammonia TSand 9volumes of a 0.2%solution of hydroxylamine hydrochloride.Immediately shake both solutions vigorously for 1minute.Any red color in the test solution is not more intense than that in the Standard solution (5µg per g).
Organic volatile impurities,Method IVá467ñ: meets the requirements.
Content of silicon dioxide Transfer 3.00g of Simethicone to a screw-capped bottle,add 10.0mLof n-hexane,cap,and mix by shaking (Test solution).Prepare aStandard solution by similarly treating a 3.00-g portion of USP Simethicone RS.Prepare aDimethicone preparation by similarly treating a 3.00-g portion of dimethicone having a viscosity of 500centistokes.Using an IRspectrophotometer and 0.1-mm cells,determine the absorbance spectra of well-mixed portions of theTest solution,theStandard solution,and theDimethicone preparation between 7and 9µm,using n-hexane as the blank.Determine the absorbances of theTest solution,theStandard solution,and theDimethicone preparation at the wavelength of minimum absorbance at about 8.2µm observed in the spectrum obtained from theDimethicone preparation.Calculate the percentage of silicon dioxide in the Simethicone taken by the formula:
C(AU-AD)/(AS-AD),in whichCis the designated percentage of silicon dioxide in USP Simethicone RS,AUis the absorbance of theTest solution,ADis the absorbance of theDimethicone preparation,andASis the absorbance of theStandard solution.
Assay Transfer about 50mg of Simethicone,accurately weighed,to a round,narrow-mouth,screw-capped,120-mLbottle,add 25.0mLof toluene,and swirl to disperse.Add 50mLof dilute hydrochloric acid (2in 5),close the bottle securely with a cap having an inert liner,and shake for 5minutes,accurately timed,on a reciprocating shaker at a suitable rate (e.g.,about 200oscillations per minute and a stroke of 38±2mm).Transfer the mixture to a 125-mLseparator,and remove about 5mLof the upper organic (toluene)layer to a 15-mLscrew-capped test 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 aStandard preparation by similarly treating a 25.0-mLportion of a solution of USP Polydimethylsiloxane RSin toluene having a known concentration of about 2mg per mL.Prepare a procedural blank by similarly treating 25.0mLof toluene.Concomitantly determine the absorbances of the solutions in 0.5-mm cells at the wavelength of maximum absorbance at about 7.9µm,with an IRspectrophotometer,using the blank to set the instrument.Calculate the quantity,in mg,of [-(CH3)2SiO-]nin the Simethicone taken by the formula:
25C(AU/AS),in whichCis the concentration,in mg per mL,of USP Polydimethylsiloxane RSin theStandard preparation,andAUandASare the absorbances of theAssay preparation and theStandard preparation,respectively.
Auxiliary Information Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28NF23Page 1768Pharmacopeial Forum:Volume No.30(4)Page 1293