CINNARIZINE SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of the Cinnarizine from the
Pharmacopoeial specifications.
2.0 SCOPE:
This
SOP shall be applicable in Q.C laboratory.
3.0 RESPONSIBILITY:
3.1 Q.C Analysts.
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 powder.
5.1.2
Solubility:
5.1.2.1 Material and equipment:
5.1.2.1.1
Glassware
(5 test tubes, 1 spatula, 1 pipette).
5.1.2.1.2
Ethanol
(96%).
5.1.2.1.3
Methylene
chloride.
5.1.2.1.4
Acetone.
5.1.2.1.5
Methanol.
5.1.2.1.6
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
5 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
methylene chloride in test tube 2 and observe.
5.1.2.3.4
Add
acetone in test tube 3 and observe.
5.1.2.3.5
Add
ethanol (96%) in test tube 4 and observe.
5.1.2.3.6
Add
methanol in test tube 5 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 methylene chloride is freely soluble.
5.1.2.4.3
The
sample in test tube 3 containing with acetone is soluble.
5.1.2.4.4
The
sample in test tube 4 & 5 containing with ethanol (96%) and methanol is slightly
soluble.
5.2 Identification
tests:
5.2.1
Melting point:
5.2.1.1 Material and equipment:
5.2.1.1.1
Glassware
(test tubes, spatula).
5.2.1.1.2
Melting
point apparatus.
5.2.1.1.3
Capillary
tubes.
5.2.1.2 Sample:
5.2.1.2.1
Small
quantity.
5.2.1.3 Method:
5.2.1.3.1
Introduce
the sufficient quantity of sample into a capillary tube.
5.2.1.3.2
Set
the apparatus and immerse the capillary tube into the apparatus such that the
closed end is near the centre of the bulb of thermometer.
5.2.1.3.3
Switch
on the melting point apparatus.
5.2.1.3.4
Operate
the melting point apparatus.
5.2.1.3.5
Raise
the temperature of the apparatus.
5.2.1.3.6
Record
the temperature at which the last particle passes into the liquid phase.
5.2.1.3.7
Record
measurements in annexure-1.
5.2.1.4 Observations:
5.2.1.4.1
The
melting point of Cinnarizine is 118oC to 122oC.
5.2.2
5.2.2.1 Material and equipment:
5.2.2.1.1
Glassware
(test tubes, spatula).
5.2.2.1.2
Water
bath.
5.2.2.1.3
0.2g
of anhydrous citric acid.
5.2.2.1.4
10.0ml
of acetic anhydride.
5.2.2.2 Sample:
5.2.2.2.1
20.0mg.
5.2.2.3 Method:
5.2.2.3.1
Take
a test tube and add 0.2g of anhydrous citric acid in 10.0ml of acetic
anhydride.
5.2.2.3.2
Dissolve
it in water-bath at 80oC and maintain the temperature of the
water-bath at 80oC for 10min.
5.2.2.3.3
Add
about 20mg of the substance to be examined.
5.2.2.3.4
Observe
the changes.
5.2.2.4 Observations:
5.2.2.4.1
A
purple color develops.
5.3 Loss
on drying:
5.3.1
Material
and equipment:
5.3.1.1 Glassware (according to requirement).
5.3.1.2 Desiccator.
5.3.1.3 Diphosphorous pentaoxide.
5.3.1.4 Analytical weighing balance.
5.3.1.5 Spatula.
5.3.2
Sample:
5.3.2.1 1.0g.
5.3.3
Method:
5.3.3.1 Weigh 1g of the test sample.
5.3.3.2 Set the desiccator apparatus with
desiccant.
5.3.3.3 Place the sample into the china dish or
petri dish.
5.3.3.4 Set the temperature 60oC and at
1.5kPa to 2.5kPa pressure for at least 4h.
5.3.3.5 And wait till the sample loses its
moisture.
5.3.3.6 After 4h weigh the sample again by using
analytical weighing balance i.e. the final weight.
5.3.3.7 Note down readings on given Annexure-2.
5.3.4
Observations:
5.3.4.1 Maximum 0.5%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1 Glassware (according to requirement).
5.4.1.2 Titration apparatus.
5.4.1.3 Water-bath.
5.4.2
Material and reagents:
5.4.2.1 Anhydrous acetic acid.
5.4.2.2 Methyl ethyl ketone.
5.4.2.3 0.2ml of naphtholbenzein solution (as an
indicator).
5.4.2.4 0.1M Perchloric acid.
5.4.3
Sample:
5.4.3.1 0.150g.
5.4.4
Method of analysis:
5.4.4.1 Sample titration:
5.4.4.1.1
Take
a titration flask and add in it 0.150g of sample.
5.4.4.1.2
Add
50.0ml of a mixture of 1 volume of anhydrous acetic acid and 7 volumes of
methyl ethyl ketone. Dissolve it by using magnetic stirrer operate.
5.4.4.1.3
Set
titration apparatus.
5.4.4.1.4
Use
0.2ml of naphtholbenzein solution as indicator.
5.4.4.1.5
Titrate
with 0.1M Perchloric acid.
5.4.4.1.6
Note
down the volume used as shown in Annexure-3.
5.4.4.1.7
And
take average.
5.4.4.2 Blank titration:
5.4.4.2.1
Take
a titration flask and add 50.0ml of a mixture of 1 volume of anhydrous acetic
acid and 7 volumes of methyl ethyl ketone. Dissolve it by using magnetic
stirrer.
5.4.4.2.2
Set
titration apparatus.
5.4.4.2.3
Use
0.2ml of naphtholbenzein solution as indicator.
5.4.4.2.4
Titrate
with 0.1M Perchloric acid.
5.4.4.2.5
Note
down the volume used as shown in Annexure-3.
5.4.4.2.6
And
take average.
5.4.4.3 Calculate percentage purity.
5.4.4.4 Calculations:
5.4.4.4.1
After
taking average volume of both blank titration and sample titration. Calculate
the volume used by the examined substance by using formula:
Volume
used by substance = Blank titration - Sample titration.
5.4.4.4.2
For
percentage purity use formula:
%age
purity = volume used by substance x factor x 100
Weight of sample
5.4.4.4.3
Put
values and calculate %age purity.
5.4.5
Factor:
5.4.5.1 1ml of 0.1M Perchloric acid is equivalent
to 18.43mg of C26H28N2.
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 I., Official Monograph / Cinnarizine: 2015, pp. 559-560.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: Observations
of percentage loss of drying.
Annexure 3: Observations
and calculations of assay.
Annexure:
1
Observations
of Melting point apparatus
Melting
point apparatus
Sample
= _____________
Time
period = _____________
Average:
_____________
Result:
_________________
Remarks:
____________________________________________________________
_____________________________________________________________________
|
Annexure: 2
Observations
of percentage loss of drying
Percentage loss
of drying
Apparatus:
____________________
Temperature:
__________________
Pressure:
_____________________
Weight
of Sample = _____________
Time
period = _____________
Average
% Loss of Moisture: _____________
Remarks:
____________________________________________________________
|
||||||||||||||||||||||||
Annexure:
3
Observations
and calculations of assay
Indicator:
___________________
Weight
of sample: ____________
Factor: _____________
Titrant:
_____________________
Sample titration
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
1.
|
|||
2.
|
|||
3.
|
Average volume: _________________
Blank titration
Sr.#
|
Initial volume (vi)
(ml)
|
Final volume (vf)
(ml)
|
vf-vi
(ml)
|
1.
|
|||
2.
|
|||
3.
|
Average volume: _________________
Calculations:
Volume used by substance
= Blank titration - Sample titration.
%age purity = volume
used by substance x factor x 100
Weight of sample
Result:
____________________________________________________________________
9.0 ABBREVIATIONS:
Abbreviation
|
Expanded Form
|
SOP
|
Standard
operating procedure
|
&
|
And
|
No.
|
Number
|
Ltd.
|
Limited
|
Q.C
|
Quality
control
|
B.P
|
British
pharmacopoeia
|
mg
|
Milligram
|
ml
|
Milliliter
|
g
|
Grams
|
Vol
|
Volume
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
%
|
Percentage
|
B.P
|
British
pharmacopoeia
|
oC
|
Degree
centigrade
|
M
|
Molar
|
vi
|
Initial
volume
|
vf
|
Final
volume
|
h
|
Hours
|
Ti
|
Initial
temperature
|
Tf
|
Final
temperature
|