SIMETICONE METHOD OF ANALYSIS SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Simeticone from the
Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1
Q.C Analyst.
4.0 ACCOUNTABILITY:
4.1
Q.C Manager.
5.0 PROCEDURE:
5.1 Characters:
5.1.1
Appearance:
5.1.1.1
Viscous,
grayish-white, opalescent liquid.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (7 test
tubes, 1 spatula, 1 pipette).
5.1.2.1.2
Anhydrous ethanol.
5.1.2.1.3
Ethyl acetate.
5.1.2.1.4
Methylene
chloride.
5.1.2.1.5
Methyl ethyl
ketone.
5.1.2.1.6
Toulene.
5.1.2.1.7
Purified water.
5.1.2.1.8
Methanol.
5.1.2.2
Sample:
5.1.2.2.1
Small quantity.
5.1.2.3
Method:
5.1.2.3.1
Take 7 test tubes
and add small quantity of sample for testing solubility according to B.P
specifications.
5.1.2.3.2
Add purified water
in test tube 1 and observe.
5.1.2.3.3
Add anhydrous
ethanol in test tube 2 and observe.
5.1.2.3.4
Add Methanol in
test tube 3 and observe.
5.1.2.3.5
Add Ethyl acetate
in test tube 4 and observe.
5.1.2.3.6
Add Methylene
chloride in test tube 5 and observe.
5.1.2.3.7
Add Methyl ethyl
ketone in test tube 6 and observe.
5.1.2.3.8
Add Toulene in
test tube 7 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 containing with purified water is practically insoluble.
5.1.2.4.2
The sample in test
tube 2 containing with anhydrous ethanol is very slightly soluble or
practically insoluble.
5.1.2.4.3
The sample in test
tube 3 containing with Methanol is practically insoluble.
5.1.2.4.4
The sample in test
tube 4, 5, 6 & 7 containing with ethyl acetate, Methylene chloride, Methyl
ethyl ketone and toluene is partly miscible.
5.2 Identification
tests:
5.2.1
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware (2 test
tubes, 1 pipette, 1 spatula).
5.2.1.1.2
Analytical
weighing balance.
5.2.1.1.3
Burner.
5.2.1.1.4
Water-bath.
5.2.1.1.5
1.0ml of a 1g/L
solution of chromotropic acid, sodium salt R in sulfuric acid.
5.2.1.2
Sample:
5.2.1.2.1
0.5g.
5.2.1.3
Method:
5.2.1.3.1
Take test tube A
and add in it 0.5g of sample in it.
5.2.1.3.2
Heat it over a
small flame until white fumes begin to appear.
5.2.1.3.3
Take test tube B
containing 1.0ml of a 1g/L solution of chromotropic acid, sodium salt R in
sulfuric acid.
5.2.1.3.4
Invert the test
tube A over a test tube B, so that the fumes reach the solution.
5.2.1.3.5
Shake the test
tube B for about 10s and eat on water-bath for 5min.
5.2.1.3.6
Observe the
changes.
5.2.1.4
Observations:
5.2.1.4.1
The solution is
violet.
5.2.2
Silicates
test:
5.2.2.1
Material and equipment:
5.2.2.1.1
Glassware (1
spatula, 1 pipette, 1 crucible, 1 copper wire).
5.2.2.1.2
Water-bath.
5.2.2.1.3
10.0mg of sodium
fluoride.
5.2.2.1.4
Sulfuric acid.
5.2.2.1.5
Purified water.
5.2.2.2
Sample:
5.2.2.2.1
The residue
obtained in the test for silica under assay 5.3.
5.2.2.3
Method:
5.2.2.3.1
Take a lead or a
platinum crucible add in it prescribed quantity of the substance, mix it by
means of a copper wire with about 10.0mg of sodium fluoride and a few drops of
Sulfuric acid to give a thin slurry.
5.2.2.3.2
Cover the crucible
with a thin, transparent plate of plastic under which a drop of purified water
is suspended and warm it gently on water bath.
5.2.2.3.3
Observe the
changes.
5.2.2.4
Observations:
5.2.2.4.1
Within a short
time a white ring is rapidly formed around the drop of purified water. (7.1) (7.2)
5.3 Assay:
5.3.1
IR
absorption Spectrophotometry:
5.3.1.1
Material and equipment:
5.3.1.1.1
Glassware
(according to requirement).
5.3.1.1.2
IR
Spectrophotometer.
5.3.1.1.3
Magnetic stirrer.
5.3.1.1.4
2mg/ml of USP
Polydimethylsiloxane RS.
5.3.1.1.5
Toluene.
5.3.1.1.6
Dilute
hydrochloric acid.
5.3.1.1.7
Anhydrous sodium
sulfate.
5.3.1.2
Sample:
5.3.1.2.1
50.0mg.
5.3.1.3
Standard stock solution:
5.3.1.3.1
Take a beaker and
prepare standard stock solution according to need 2mg/ml of USP
Polydimethylsiloxane RS in toluene.
5.3.1.4
Standard solution:
5.3.1.4.1
Take a round,
narrow-mouth, screw-capped 120.0ml of bottle and add 25.0ml of standard stock
solution in it.
5.3.1.4.2
Add 50.0ml of
dilute hydrochloric acid (2 in 5) in it, close the bottle securely with a cap
having an inert liner, and shake for 5min , accurately timed , on a
reciprocating shaker at a suitable rate (e.g. about 200 oscillations/min and a
stroke of 38±2mm).
5.3.1.4.3
Transfer the
mixture to a 125.0ml separator, and remove 5.0ml of the upper organic (toluene)
layer to a 15.0ml, screw-capped test tube containing 0.5g of anhydrous sodium
sulfate.
5.3.1.4.4
Close the tube
with a screw-cap having an inert liner, agitate vigorously, and centrifuge the
mixture until a clear supernatant is obtained.
5.3.1.5
Sample stock solution:
5.3.1.5.1
Take a round,
narrow-mouth, screw-capped 120.0ml of bottle and add 50.0mg of Simeticone.
5.3.1.5.2
Add 25.0ml of
toluene and swirl to disperse by using magnetic stirrer.
5.3.1.6
Sample solution:
5.3.1.6.1
Take a round,
narrow-mouth, screw-capped 120.0ml of bottle and add 50.0mg of Simeticone.
5.3.1.6.2
Add 25.0ml of
toluene and swirl to disperse by using magnetic stirrer.
5.3.1.6.3
Add 50.0ml of
dilute hydrochloric acid (2 in 5) in it, close the bottle securely with a cap
having an inert liner, and shake for 5min , accurately timed , on a
reciprocating shaker at a suitable rate (e.g. about 200 oscillations/min and a
stroke of 38±2mm).
5.3.1.6.4
Transfer the
mixture to a 125.0ml separator, and remove 5.0ml of the upper organic (toluene)
layer to a 15.0ml, screw-capped test tube containing 0.5g of anhydrous sodium
sulfate.
5.3.1.6.5
Close the tube
with a screw-cap having an inert liner, agitate vigorously, and centrifuge the
mixture until a clear supernatant is obtained.
5.3.1.7
Blank:
5.3.1.7.1
Take a round,
narrow-mouth, screw-capped 120.0ml of bottle and add 25.0ml of toluene.
5.3.1.7.2
Add 50.0ml of
dilute hydrochloric acid (2 in 5) in it, close the bottle securely with a cap
having an inert liner, and shake for 5min , accurately timed , on a reciprocating
shaker at a suitable rate (e.g. about 200 oscillations/min and a stroke of
38±2mm).
5.3.1.7.3
Transfer the
mixture to a 125.0ml separator, and remove 5.0ml of the upper organic (toluene)
layer to a 15.0ml, screw-capped test tube containing 0.5g of anhydrous sodium
sulfate.
5.3.1.7.4
Close the tube
with a screw-cap having an inert liner, agitate vigorously, and centrifuge the
mixture until a clear supernatant is obtained.
5.3.1.8
Instrumental conditions:
5.3.1.8.1
Mode:
IR.
5.3.1.8.2
Analytical
wavelength: Wavelength of maximum absorbance at about
7.9μm.
5.3.1.8.3
Cell:
0.5mm.
5.3.1.9
Method of analysis:
5.3.1.9.1
Samples:
Standard
stock solution, Standard solution, Sample stock solution and Sample solution.
5.3.1.9.2
Switch ON the IR
spectrophotometer and operate it according to SOP No. BM/QCEO/SOP024-00.
5.3.1.9.3
Determine the absorbance
of the samples, using the Blank to set the instrument.
5.3.1.9.4
Calculate the
percentage of the Polydimethylsiloxane [-(CH3)2SiO-]n
in the portion of Simeticone taken:
Result: (AU/AS) x (CS/CU)
x 100
AU
= absorbance of the sample solution.
AS
= absorbance of the standard solution.
CS
= concentration of USP Polydimethylsiloxane RS in the standard stock
solution (mg/ml).
CU
= concentration of simethicone in the sample stock solution (mg/ml).
5.3.1.10 Acceptance
criteria:
5.3.1.10.1 90.5%-99.0%.
(7.3)
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1
The British Pharmacopoeia. Vol II., Official Monograph /Simeticone: 2015, pp. 810-811.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
7.3
USP38NF33
Volume-6 Official Monograph/ Simethicone: 2015, pp.: 5295-5296.
8.0 ANNEXURES:
Annexure 1: Calculations
of IR-spectrophotometer
Annexure:
1
Calculations
of IR-spectrophotometer
|
IR-spectrophotometer
Model:
_____________________________ Date:
_________________
OBSERVATIONS:
Blank solution:
Standard solution:
Sample solution:
CALCULATIONS:
Result: (AU/AS) x (CS/CU)
x 100
Results:
_______________
Remarks:
______________________________________________________________
|
9.0 ABBREVIATIONS:
|
Abbreviation
|
Expanded Form
|
|
SOP
|
Standard
operating procedure
|
|
&
|
And
|
|
No.
|
Number
|
|
Ltd.
|
Limited
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
Format
|
|
Q.C
|
Quality
control
|
|
Vol
|
Volume
|
|
BP
|
British
Pharmacopoeia
|
|
mg
|
Milligram
|
|
ml
|
Milliliter
|
|
M
|
Molar
|
|
g
|
Grams
|
|
s
|
Seconds
|
|
Min
|
Minute
|
|
%
|
Percentage
|
|
R
|
Reagent
|
|
oC
|
Degree
centigrade
|
|
IR
spectrophotometer
|
Infrared
spectrophotometer
|
|
mg/ml
|
Milligram
per milliliter
|
|
USP
|
United
states pharmacopoeia
|
|
RS
|
Reference
standard
|
|
NF
|
National
formulary
|
|
μm
|
Micrometer
|
|
mm
|
Millimeter
|
|
g/L
|
Grams
per liter
|