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Simethicone Powder CTD 3.2.P/2.5

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3.2.P.5.2 Analytical Procedures

Appearance
Examine visually
Acceptance criteria: White powder

Identification
Infrared absorption <197S>
The IR absorption spectrum of the Sample solution exhibits maxima at the same wavelengths as
that of the Standard solution, prepared as directed in the Assay.

Particle size
Use the US No. 20 (850 m) and US No. 35 (500 m) sieves. Place 10.0 g of powders, accurately
weighed, on the uppermost sieve which is placed on the other sieve described above and a close-
fitting receiving pan and is covered with a lid. Shake the sieves in a horizontal direction for 3
minutes, and tap gently at intervals. Weigh the amount of powders remaining on each sieve and
in the receiving pan.

Acceptance criteria:
- US Sieve No. 20 (850 m): passes completely
- US Sieve No. 35 (500 m): NMT 5.0% is retained

Loss on Drying
Sample: 1g
Analysis: Dry the Sample at 200°C for 4hours.

Acceptance criteria: NMT 5.0%

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3.2.P.5.2 Analytical Procedures (continued)

Assay
Sample solution: Transfer an accurately weighed portion of the powder, equivalent to about
50mg of Simethicone, to a separating funnel. Add 25.0 mL of toluene, and shake for 1 hour on a
separating funnel shaker at 300rpm. Add 50 mL of dilute hydrochloric acid (2 in 5), and shake
for 1 hour on a separating funnel shaker at 300rpm. Allow to stand for about 2 hours for the
layer separation. Transfer 10mL of the toluene layer to a 15mL screw-capped test tube
containing 1g 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 is obtained.

Standard solution: Transfer about 50mg of Polydimethylsiloxane standard, accurately weighed,

to a 50mL volumetric flask. Add 25mL of toluene and dissolve in.

Analysis conditions
Mode: IR
Analytical Wavelength: Wavelength of maximum absorbance at about 7. m
Cell size: 0.5mm
Blank: Toluene

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3.2.P.5.2 Analytical Procedures (continued)

Assay (continued)
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of polydimethylsiloxane in the portion of the sample taken:
Result = (AU / AS) x (CS / CU) x Assay of Standard (%)
In which,
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = amount of Standard taken (mg)
CU = amount of Sample taken (mg)

Acceptance criteria: 57.0 ~ 66.5% as polydimethylsiloxane

Purity
1) Heavy metals
Sample solution: Place about 1.0g of Sample in a quartz or porcelain crucible, cover loosely
with a lid, and carbonize by gentle ignition. After cooling, add 2mL of nitric acid and 5 drops of
sulfuric acid, heat cautiously until white fumes are no longer evolved, and incinerate by ignition
between 500ºC and 600ºC. Cool, add 2mL of hydrochloric acid, evaporate to dryness on a water
bath, moisten the residue with 3 drops of hydrochloric acid, add 10mL of hot water, and warm
for 2 minutes. Then add 1 drop of phenolphthalein TS, add ammonia TS dropwise until the
solution develops a pale red color, add 2mL of dilute acetic acid, filter if necessary, and wash
with 10mL of water. Transfer the filtrate and washings to a Nessler tube, and add water to make
50mL.

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3.2.P.5.2 Analytical Procedures (continued)

Purity (continued)
1) Heavy metals (continued)
Control solution: Evaporate a mixture of 2mL of nitric acid, 5 drops of sulfuric acid, and 2mL of
hydrochloric acid on a water bath, further evaporate to dryness on a sand bath, and moisten the
residue with 3 drops of hydrochloric acid. Hereinafter, proceed as directed in the Sample
solution, then add 2.0mL of Standard Lead Solution and water to make 50mL.

Procedure
Add 1 drop of sodium sulfide TS to each of the sample solution and the control solution, mix
thoroughly, and allow to stand for 5 minutes. Then compare the colors of both solutions by
viewing the tubes downward or transversely against a white background. The sample solution
has no more color than the control solution.

Acceptance criteria: NMT 20ppm

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3.2.P.5.2 Analytical Procedures (continued)

Purity (continued)
2) Arsenic
Sample solution: Weigh about 1.0g of the sample and place it in a crucible of platinum, quartz
or porcelain. Add 10mL of a solution of magnesium nitrate in ethanol (1 in 50), ignite the
ethanol and heat gradually to incinerate. If carbonized material still remains by this procedure,
moisten with a small quantity of nitric acid, and ignite again to incinerate. After cooling, add
3mL of hydrochloric acid, heat on a water bath to dissolve the residue, and designate it as the
sample solution.

Control solution: Measure accurately 2mL of standard arsenic solution in the generator bottle A.
Add 5mL of diluted hydrochloric acid (1 in 2) and 5mL of potassium iodide TS, and allow to
stand for 2 to 3 minutes. Add 5mL of acidic stannous chloride TS, allow to stand at room
temperature for 10 minutes, and then proceed as directed above. The color produced
2O3) and is used as the standard.

Procedure
Unless otherwise specified, proceed as directed in the following procedure. Carry out the
preparation of the standard color at the same time. Place the sample solution in the generator
bottle A and, if necessary, wash down the solution in the bottle with a small quantity of water.
Add 1 drop of methyl orange TS, and after neutralizing with ammonia TS, ammonia solution
(28) or dilute hydrochloric acid, add 5mL of diluted hydrochloric acid (1 in 2) and 5mL of
potassium iodide TS, and allow to stand 2 to 3 minutes. Add 5mL of acidic tin (II) chloride TS,
and allow to stand for 10 minutes.

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3.2.P.5.2 Analytical Procedures (continued)

Purity (continued)
2) Arsenic (continued)
Procedures (continued)
Then add water to make 40mL, add 2 g of zinc for arsenic analysis, and immediately connect the
rubber stopper H fitted with B and C with the generator bottle. Transfer 5mL of the absorbing
solution for hydrogen arsenide to the absorber tube D, insert the tip of C to the bottom of the
absorber tube D, then immerse the generator bottle A up to the shoulder in water maintained at
25°C, and allow to stand for 1 hour.
Disconnect the absorber tube, add pyridine to make 5mL, if necessary, and observe the color of
the absorbing solution: the color produced is not more intense than the standard color.

Apparatus
Use the apparatus illustrated in Figure. Place glass wool F in the exit tube B up to about 30mm
in height, moisten the glass wool uniformly with a mixture of an equal volume of lead acetate
TS and water, and apply gentle suction to the lower end to remove the excess of the mixture.
Insert the tube vertically into the center of the rubber stopper H and attach the tube to the
generate bottle A so that the small perforation E in the lower and of B extends slightly below. At
the upper end of B, attach the rubber stopper I to hold the tube C vertically. Make the lower end
to the exit tube of C level with that of the rubber stopper I.

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3.2.P.5.2 Analytical Procedures (continued)

Purity (continued)
2) Arsenic (continued)
Apparatus (continued)

Figure. Apparatus for the Arsenic Limit test (The figure are in mm)
A: Generator bottle (capacity up to the shoulder: approcimately 70mL)
B: Exit tube
C: Glass tube (inside diameter: 5.6mm, the tip of the part to be inserted in the absorber tube D is
drawn out to 1mm in diameter)
D: Absorber tube (inside diameter: 10mm)
E: Small perforation
F: Glass wool (about 0.2g)
G: Mark of 5mL
H,I: Ruber stoppers

Acceptance criteria: NMT 2ppm

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3.2.P.5.2 Analytical Procedures (continued)

Microbial limit test

Proceed as directed in the USP General Chapters: Microbial Enumeration Tests <61> and Tests
for Specified Microorganisms <62>: It meets the requirements of the tests for absence of
Salmonella species, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The
total aerobic microbial count does not exceed 1000cfu/g; and the total combined molds and
yeasts count does not exceed 100cfu/g.

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