MEBEVERINE
HYDROCHLORIDE SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Mebeverine Hydrochloride 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
White or almost
white.
5.1.1.2
Crystalline
powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (3 test
tubes, 1 spatula, 1 pipette).
5.1.2.1.2
Ethanol (96%).
5.1.2.1.3
Ether.
5.1.2.1.4
Purified water.
5.1.2.2
Sample:
5.1.2.2.1
Small quantity.
5.1.2.3
Method:
5.1.2.3.1
Take 3 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 Ethanol (96%) in
test tube 2 and observe.
5.1.2.3.4
Add ether in test
tube 3 and observe
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1containing with purified water is very soluble.
5.1.2.4.2
The sample in test
tube 2 containing with Ethanol (96%) is freely soluble.
5.1.2.4.3
The sample in test
tube 2 containing with ether is practically insoluble.
5.2 Identification
tests:
5.2.1
Chlorides
test:
5.2.1.1
Material and equipment:
5.2.1.1.1
Glassware (test
tube, spatula, beaker, glass rod).
5.2.1.1.2
Centrifugation
machine.
5.2.1.1.3
2M nitric acid.
5.2.1.1.4
Purified water.
5.2.1.1.5
0.4ml of Silver
nitrate R1.
5.2.1.1.6
Ammonia.
5.2.1.2
Sample:
5.2.1.2.1
25.0mg.
5.2.1.3
Method:
5.2.1.3.1
Take a test tube
add in it 2.0ml of water with the help of pipette.
5.2.1.3.2
Add 25.0mg of
sample and dissolve it.
5.2.1.3.3
Acidify it with 2M
nitric acid.
5.2.1.3.4
Centrifuge it in
centrifugation machine, according to SOP.
5.2.1.3.5
The supernatant
liquid is produced; add 0.4ml of silver nitrate solution R1 in it.
5.2.1.3.6
Shake and allow it
to stand.
5.2.1.3.7
A curdled, white
ppt is formed.
5.2.1.3.8
Centrifuge it
again in centrifugation machine, according to SOP.
5.2.1.3.9
The obtained ppt
is wash with 3 quantities, each of 1ml, of water.
5.2.1.3.10 Carry
out this operation rapidly is subdued light, degrading the fact that the
supernatant solution may not become perfectly clear.
5.2.1.3.11 Suspend
the precipitate in 2.0ml of water and add 1.5ml of ammonia
5.2.1.4
Observations:
5.2.1.4.1
The precipitate
dissolves easily with the possible exception of a few large particles which
dissolves slowly.
5.3 Loss
on drying:
5.3.1
Material and equipment:
5.3.1.1
Glassware
(according to requirement).
5.3.1.2
Analytical
weighing balance.
5.3.1.3
Oven.
5.3.2
Sample:
5.3.2.1
1.0g.
5.3.3
Method:
5.3.3.1
Weigh 1.0g of the
test sample.
5.3.3.2
Set the oven
apparatus. Operate it according to the SOP.
5.3.3.3
Place the sample
into the tray and dry it.
5.3.3.4
Set the
temperature of oven at 105oC for at least 1 hour.
5.3.3.5
And wait till the
sample loses its moisture.
5.3.3.6
After 1 hour weigh
the sample again by using analytical weighing balance i.e. the final weight.
5.3.3.7
Note down readings
on given Annexure-1.
5.3.4
Observation:
5.3.4.1
Loses not more
than 0.5% of its weight.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1
Glassware
(according to requirement).
5.4.1.2
Potentiometer.
5.4.1.3
Magnetic stirrer.
5.4.2
Material
and reagents:
5.4.2.1
7.0ml of mercury
(II) acetate solution.
5.4.2.2
0.1M Perchloric
acid.
5.4.3
Sample:
5.4.3.1
0.4g.
5.4.4
Method
of analysis:
5.4.4.1 Take
a 50.0ml of beaker and add 0.4g of sample in it.
5.4.4.2 And
add 7.0ml of mercury (II) acetate solution.
5.4.4.3 Fill
the right hand side burette with titrant 0.1M Perchloric acid.
5.4.4.4 Carry
out a Potentiometric titration.
5.4.4.5 Operate
potentiometer according to SOP.
5.4.4.6 To
neutralize analyte add titrant fixed volume (1ml, 0.5ml or 0.1ml) from burette
every time note the reading of change in potential difference (millivolts) for
each addition in given annexure-2.
5.4.4.7 Plot
a graph, volume used v/s millivolts.
5.4.4.8 Find
out the END POINT.
5.4.4.9 Peak
of graph indicates END POINT i.e. the point at which maximum millivolts. Note
down volume used at that point.
5.4.4.10 Perform
blank titration without using sample. Similarly, as sample titration performed.
Record observations in annexure-2.
5.4.4.11 Calculate
volume used by substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.4.4.12 Calculate
percentage purity of the sample by using formula:
%age purity = volume used by
substance x factor x 100
Weight
of sample
5.4.5
Factor:
5.4.5.1 Each
ml of 0.1M Perchloric acid VS is equivalent to 46.60mg of Mebeverine hydrochloride C25H35NO5.HCl.
5.4.6
Limit:
5.4.6.1
99.0% to 101.0% (dried
substance).
6.0 REVISION LOG:
|
Revision No.
|
Effective Date
|
Reason
|
|
00
|
|
New SOP
|
7.0 REFERENCES:
7.1
The British
Pharmacopoeia. Vol II.,
Official Monograph / Mebeverine
hydrochloride: 2015, pp. 194-195.
7.2
The British
Pharmacopoeia. Vol V.,
Official Monograph /Qualitative Reactions and Tests: 2015, pp. 266-270.
8.0 ANNEXURES:
Annexure 1: Observations
of Percentage Loss of drying by using oven.
Annexure 2: Assay
observations and calculations (Potentiometric titration).
Annexure:
1
Observations
of percentage loss of drying by using Oven
|
Percentage
loss of drying by using Oven
Weight
of Sample = _____________
Time
period = _____________
Pressure=
_________________
Average % Loss of Moisture: _____________
Remarks:
_______________________________________________________________
|
||||||||||||||||||||||||
Annexure:
2
Assay
observations and calculations (Potentiometric titration)
|
Potentiometric titration
Reference
electrode: ___________________
Indicator
electrode: ____________________
Speed
of magnetic stirrer: _______________
Titrant
used: __________________________
Indicator:
____________________________
Blank
titration:
Plot a graph, volume used v/s millivolts and find out peak
of graph i.e. END POINT of blank titration.
Sample
titration:
Plot a graph, volume used v/s millivolts and find out peak
of graph i.e. END POINT of sample titration:
Volume used by Blank titration: __________________
Volume used by Sample titration: _________________
Volume used by substance = Blank titration - Sample
titration.
mV used by Blank titration: __________________
mV used by Sample titration: _________________
mV used by substance = Blank
titration - Sample titration.
Volume
used by substance: _______________________
Voltmeter
(mV) used by substance: _________________
RESULT: ____________________________________________________________
|
9.0 ABBREVIATIONS:
|
Abbreviation
|
Expanded Form
|
|
SOP
|
Standard
operating procedure
|
|
&
|
And
|
|
No.
|
Number
|
|
Ltd.
|
Limited
|
|
QCA
|
Quality
control active ingredient
|
|
F
|
FOormat
|
|
Q.C
|
Quality
control
|
|
Vol
|
Volume
|
|
%
|
Percentage
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
M
|
Molar
|
|
g/L
|
Grams
per liter
|
|
mg
|
Milligram
|
|
B.P
|
British
pharmacopoeia
|
|
oC
|
Degree
centigrade
|
|
R
|
Reagent
|
|
v/s
|
Verses
|
|
mV
|
Millivolts
|
|
H
|
Hours
|