DICLOFENAC SODIUM SOP
1.0 OBJECTIVE:
To
lay down a procedure of analytical report for the active raw material of the
Diclofenac Sodium 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 slightly yellowish.
5.1.1.2 Slightly hygroscopic.
5.1.1.3 Crystalline powder.
5.1.2
Solubility:
5.1.2.1 Material and equipment:
5.1.2.1.1
Glassware
(test tubes, spatula).
5.1.2.1.2
Methanol.
5.1.2.1.3
Ethanol
(96%).
5.1.2.1.4
Acetone.
5.1.2.1.5
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
4 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
methanol in test tube 2 and observe.
5.1.2.3.4
Add
ethanol (96%) in test tube 3 and observe.
5.1.2.3.5
Add
acetone in test tube 4 and observe.
5.1.2.4 Observations:
5.1.2.4.1
The
sample in test tube 1 containing with water is sparingly soluble.
5.1.2.4.2
The
sample in test tube 2 containing with methanol is freely soluble.
5.1.2.4.3
The
sample in test tube 3 containing with ethanol (96%) is soluble.
5.1.2.4.4
The
sample in test tube 4 containing with acetone is slightly soluble.
5.1.3
Melting point:
5.1.3.1 Material and equipment:
5.1.3.1.1
Glassware
(test tubes, spatula).
5.1.3.1.2
Melting
point apparatus.
5.1.3.1.3
Capillary
tubes.
5.1.3.2 Sample:
5.1.3.2.1
Small
quantity.
5.1.3.3 Method:
5.1.3.3.1
Introduce
the sufficient quantity of sample into a capillary tube.
5.1.3.3.2
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.
5.1.3.3.3
Switch
on the melting point apparatus.
5.1.3.3.4
Operate
the melting point apparatus according to the SOP
5.1.3.3.5
Raise
the temperature of the apparatus.
5.1.3.3.6
Record
the temperature at which the last particle passes into the liquid phase.
5.1.3.3.7
Record
measurements in annexure-1.
5.1.3.4 Observations:
5.1.3.4.1
The
melting point of Diclofenac sodium is about 280 oC, with
decomposition.
5.2 Identification
tests:
5.2.1
5.2.1.1 Material and equipment:
5.2.1.1.1
Glassware
(according to requirement).
5.2.1.1.2
Ethanol
(96%).
5.2.1.1.3
6g/L
solution of potassium ferricyanide.
5.2.1.1.4
9g/L
solution of ferric chloride.
5.2.1.1.5
10g/L
solution of hydrochloric acid.
5.2.1.2 Sample:
5.2.1.2.1
10.0mg.
5.2.1.3 Method:
5.2.1.3.1
Take
a test tube and add 10mg of sample in it.
5.2.1.3.2
Add
10ml of ethanol (96%) and dissolve the sample.
5.2.1.3.3
Take
1ml of this solution in another test tube and add 0.2ml of a mixture, prepared
immediately before use, equal volumes of a 6g/L solution of potassium
ferricyanide and a 9g/L solution of ferric chloride.
5.2.1.3.4
Allow
it to stand protected from light for 5min.
5.2.1.3.5
Add
3.0ml of a 10g/L solution of hydrochloric acid.
5.2.1.3.6
Allow
it to stand protected from light for 15min.
5.2.1.3.7
Observe
the changes.
5.2.1.4 Observations:
5.2.1.4.1
A
blue colour develops.
5.2.1.4.2
A
precipitate is formed.
5.2.2
Sodium test:
5.2.2.1 Material and equipment:
5.2.2.1.1
Glassware
(according to requirement).
5.2.2.1.2
Methanol.
5.2.2.1.3
Purified
water.
5.2.2.1.4
Methoxyphenylacetic
reagent.
5.2.2.1.5
Ice-water.
5.2.2.1.6
Purified
water.
5.2.2.1.7
Dilute
ammonia.
5.2.2.1.8
Ammonium
carbonate solution.
5.2.2.2 Sample:
5.2.2.2.1
60.0mg.
5.2.2.3 Method:
5.2.2.3.1
Take
a test tube and add 60.0mg of sample in it.
5.2.2.3.2
Dissolve
it in 0.5ml of methanol and 0.5ml of water.
5.2.2.3.3
Take
0.5ml of this solution in another test tube.
5.2.2.3.4
Add
1.5ml of methoxyphenylacetic reagent with the help of pipette.
5.2.2.3.5
Take
another beaker and add in it ice-water. Dip the above solution in it for 30min.
5.2.2.3.6
Observe
the changes.
5.2.2.3.7
A
voluminous, white, crystalline ppt is formed.
5.2.2.3.8
Place
test tube in the water bath at 20oC and stir for 5min.
5.2.2.3.9
The
precipitate does not disappear.
5.2.2.3.10 Add 1.0ml of the dilute ammonia in it.
5.2.2.3.11 The precipitate dissolves completely.
5.2.2.3.12 Add 1.0ml of ammonium carbonate solution.
5.2.2.3.13 Observe the changes.
5.2.2.4 Observations:
5.2.2.4.1
No
precipitate is formed.
5.3 Loss
on drying:
5.3.1.1 Material and equipment:
5.3.1.1.1
Glassware
(according to requirement).
5.3.1.1.2
Moisture
balance.
5.3.1.1.3
Analytical
weighing balance.
5.3.1.1.4
Spatula.
5.3.1.2 Sample:
5.3.1.2.1
1.0g.
5.3.1.3 Method:
5.3.1.3.1
Weigh
1g of the test sample of granules.
5.3.1.3.2
Switch
on the moisture balance.
5.3.1.3.3
Operate
the moisture balance according to the SOP.
5.3.1.3.4
Place
the sample into the aluminium dish and close the main body.
5.3.1.3.5
Set
the temperature by pressing temperature key.
5.3.1.3.6
And
wait till % of L.O.D display on the balance.
5.3.1.3.7
Note
the loss of moisture after every 5 min on the scale till two consecutive
reading shows the same loss on the scale.
5.3.1.3.8
Note
down readings on given Annexure-2.
5.3.1.4 Observations:
5.3.1.4.1
Maximum
0.5%.
5.4 Assay:
5.4.1
Apparatus:
5.4.1.1 Glassware (according to requirement).
5.4.1.2 Potentiometer.
5.4.2
Material and reagents:
5.4.2.1 Anhydrous acetic acid.
5.4.2.2 0.1M Perchloric acid.
5.4.2.3 Crystal violet solution.
5.4.3
Sample:
5.4.3.1 0.250g.
5.4.4
Method of analysis:
5.4.4.1 Take a 50.0ml of beaker and take 0.250g of
sample in it.
5.4.4.2 Add 60.0ml of anhydrous acetic acid in it
and dissolve properly.
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 using
0.1M Perchloric acid and crystal violet solution as an indicator.
5.4.4.5 Operate potentiometer according to SOP No.
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-1.
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-1.
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 1ml of 0.1M Perchloric acid is equivalent
to 31.81mg of C14H10Cl2NNaO2.
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 /
Diclofenac Sodium: 2015, pp. 733-734.
8.0 ANNEXURES:
Annexure 1: Observations
of Melting point apparatus.
Annexure 2: Observations
of percentage loss of drying.
Annexure 3:
Assay observations and calculations (Potentiometric titration)
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
Weight
of granules (Sample) = _____________
Time
period = _____________
Average
% Loss of Moisture: _____________
|
Annexure:
3
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
|
Sr.#
|
Serial
number
|
Q.C
|
Quality
control
|
%
|
Percentage
|
B.P
|
British
pharmacopoeia
|
g/L
|
Grams
per liter
|
mg
|
Milligram
|
Min
|
Minutes
|
ml
|
Milligram
|
oC
|
Degree
centigrade
|
g
|
Grams
|
M
|
Molar
|
Vol
|
Volume
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
mV
|
Millivolts
|
Ti
|
Initial
temperature
|
Tf
|
Final
temperature
|
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