CINNARIZINE SOP



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 = _____________
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
Apparatus: ____________________
Temperature: __________________
Pressure: _____________________
Weight of Sample = _____________
Time period = _____________
Sr.#
Time (min)
Weight of sample (g)
% Loss of Moisture
Initial weight
Final weight















Average % Loss of Moisture: _____________

% 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


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