DICLOFENAC SODIUM SOP


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 = _____________
Sr.#
Initial (Ti)
(oC)
Final (Tf)
(oC)
Tf - Ti
(oC)












Average: _____________

Result: _________________

Remarks: ____________________________________________________________ _____________________________________________________________________













Annexure: 2
Observations of percentage loss of drying
Percentage loss of drying
Weight of granules (Sample) = _____________
Time period = _____________
Sr.#
Time (min)
% Loss of Moisture


















Average % Loss of Moisture: _____________

% Loss of Moisture:

Optimum time for drying:












Annexure: 3
Assay observations and calculations (Potentiometric titration)
Potentiometric titration
Reference electrode: ___________________
Indicator electrode: ____________________
Speed of magnetic stirrer: _______________
Titrant used: __________________________
Indicator: ____________________________
Blank titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












Plot a graph, volume used v/s millivolts and find out peak of graph i.e. END POINT of blank titration.
Sample titration:
Sr.#
Volume used
(ml)
Voltmeter
(mV)












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


No comments:

Post a Comment