IBUPROFEN SOP

1.0  OBJECTIVE:
To lay down a procedure for the active raw material of the Ibuprofen 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 or colourless crystals.
5.1.2        Solubility:
5.1.2.1  Material and equipment:
5.1.2.1.1        Glassware (6 test tubes, 1 spatula).
5.1.2.1.2        Acetone.
5.1.2.1.3        Methanol.
5.1.2.1.4        Methylene chloride.
5.1.2.1.5        Dilute solutions of alkali hydroxides (e.g. NaOH, KOH)
5.1.2.1.6        Dilute solutions of carbonates (e.g. CaCO3).
5.1.2.1.7        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 6 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 acetone in test tube 2 and observe.
5.1.2.3.4        Add methanol in test tube 3 and observe.
5.1.2.3.5        Add methylene chloride in test tube 4 and observe.
5.1.2.3.6        Add dilute solutions of alkali hydroxides in test tube 5 and observe.
5.1.2.3.7        Add dilute solutions of carbonates in test tube 6 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, 3 & 4 containing with acetone, methanol and methylene chloride is freely soluble, respectively.
5.1.2.4.3        The sample in test tube 5 & 6 containing with dilute solutions of alkali hydroxides & dilute solutions of carbonates is dissolved, respectively.
5.2  Identification tests:
5.2.1        Melting point determination:
5.2.1.1  Material and equipment:
5.2.1.1.1        Glassware (according to requirement).
5.2.1.1.2        Melting point apparatus.
5.2.1.1.3        Capillary tubes.
5.2.1.1.4        Purified water.
5.2.1.2  Sample:
5.2.1.2.1        Sufficient quantity of sample.
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 according to the SOP
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 is 75oC-78oC.
5.2.2        UV/VIS absorption Spectrophotometry:
5.2.2.1  Material and equipment:
5.2.2.1.1        UV/VIS Spectrophotometer.
5.2.2.1.2        Glassware (according to requirement).
5.2.2.1.3        4.0g/L solution of sodium hydroxide.
5.2.2.2  Sample:
5.2.2.2.1        50.0mg.
5.2.2.3  Method:
5.2.2.3.1        Test solution:
5.2.2.3.1.1  Take a beaker of 100.0ml and add 50.0mg of sample in it.
5.2.2.3.1.2  Dissolve it in sufficient quantity of 4.0g/L solution of sodium hydroxide.
5.2.2.3.1.3  And dilute it to 100.0ml with the same alkaline solution.
5.2.2.3.2        Spectral range:
5.2.2.3.2.1  240-300nm (using a spectrophotometer with a band width of 1.0nm and a scan speed of NMT 50nm/min).
5.2.2.3.3        Absorption maxima:
5.2.2.3.3.1  At 264nm and 272nm.
5.2.2.3.4        Shoulder:
5.2.2.3.4.1  At 258nm.
5.2.2.3.5        Operate the UV/VIS spectrophotometer according to the SOP No. BM/QCEO/SOP027-00.
5.2.2.3.6        Measure the absorbance of the resulting solution at the maximum wavelength 264nm and 272nm
5.2.2.3.7        Note down values of absorbance in annexure-2.
5.2.2.3.8        Calculate the absorbance ratio A264/A258 and A272/A258.
5.2.2.4  Observations:
5.2.2.4.1        Absorbance ratio:
5.2.2.4.1.1  Absorbance ratio at A264/A258 = 1.20 to 1.30.
5.2.2.4.1.2  Absorbance ratio at A272/A258 = 1.00 to 1.10.
5.3  Other tests:
5.3.1        Optical rotation:
5.3.1.1  Material and equipment:
5.3.1.1.1        Glassware (according to the requirement).
5.3.1.1.2        Polarimeter.
5.3.1.1.3        Methanol.
5.3.1.2  Sample:
5.3.1.2.1        0.5g
5.3.1.3  Method:
5.3.1.3.1        Take a beaker of 50.0ml and add 0.5g of sample in it.
5.3.1.3.2        Add methanol in it and dissolve, dilute it to 20.0ml with the same solvent.
5.3.1.3.3        Operate the Polarimeter according to SOP.
5.3.1.3.4        Determine optical rotation on the sample solution.
5.3.1.3.5        Fill the Polarimeter tube with blank solution and determine the observed optical rotation.
5.3.1.3.6        Similarly, fill the Polarimeter tube with sample solution and determine the observed optical rotation.
5.3.1.3.7        Note down the values in annexure-3.
5.3.1.4  Observation:
5.3.1.4.1        -0.05o to +0.05o.
5.3.2        Loss on drying:
5.3.2.1  Material and equipment:
5.3.2.1.1        Glassware (according to requirement).
5.3.2.1.2        Desiccator.
5.3.2.1.3        Diphosphorous pentaoxide.
5.3.2.1.4        Analytical weighing balance.
5.3.2.1.5        Spatula.
5.3.2.2  Sample:
5.3.2.2.1        1.0g.
5.3.2.3  Method:
5.3.2.3.1        Weigh 1g of the test sample.
5.3.2.3.2        Set the desiccator apparatus with desiccant.
5.3.2.3.3        Place the sample into the china dish or petri dish.
5.3.2.3.4        Set the room temperature and at 1.5kPa to 2.5kPa pressure for at least 45min.
5.3.2.3.5        And wait till the sample loses its moisture.
5.3.2.3.6        After 45min weigh the sample again by using analytical weighing balance i.e. the final weight.
5.3.2.3.7        Note down readings on given Annexure-4.
5.3.2.4  Observations:
5.3.2.4.1        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  Magnetic stirrer.
5.4.2        Material and reagents:
5.4.2.1  50.0ml of methanol.
5.4.2.2  0.4ml of phenolphthalein solution R1 (as indicator).
5.4.2.3  0.1M sodium hydroxide.
5.4.2.4  Purified water.
5.4.3        Sample:
5.4.3.1  0.450g.
5.4.4        Method of analysis:
5.4.4.1  Sample titration:
5.4.4.1.1        Take a flask and add in it 0.450g of sample.
5.4.4.1.2        Dissolve it in 50.0ml of methanol by using magnetic stirrer.
5.4.4.1.3        Use 0.4ml of phenolphthalein solution as indicator.
5.4.4.1.4        Set titration apparatus.
5.4.4.1.5        Titrate with 0.1M sodium hydroxide, until a red colour is obtained.
5.4.4.1.6        Note down the volume used as shown in Annexure-5.
5.4.4.1.7        Take at least 3 readings and take average of it.
5.4.4.2  Blank titration:
5.4.4.2.1        Take a flask and add in it 50.0ml of methanol.
5.4.4.2.2        Use 0.4ml of phenolphthalein solution as indicator.
5.4.4.2.3        Set titration apparatus.
5.4.4.2.4        Titrate with 0.1M sodium hydroxide, until a red colour is obtained.
5.4.4.2.5        Note down the volume used as shown in Annexure-5.
5.4.4.2.6        Take at least 3 readings and take average of it.
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 sodium hydroxide is equivalent to 20.63mg of Ibuprofen C13H18O2.
5.4.6        Limit:
5.4.6.1  98.5% 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 /Ibuprofen: 2015, pp. 1191-1193.
8.0  ANNEXURES:
Annexure 1: Observations of Melting point apparatus.
Annexure 2: Observations and calculations of UV/VIS Spectrophotometer.
Annexure 3: Observations of Optical rotation.
Annexure 4: Observations of percentage loss of drying.
Annexure 5: Observations and calculations of assay.



Annexure: 1
Observations of Melting point apparatus
Sample = _____________
Time period = _____________
Sr.#
Initial (Ti)
(oC)
Final (Tf)
(oC)
Tf - Ti
(oC)












Average: _____________

Result: _________________

Remarks: _______________________________________________________________

Annexure: 2
Observations and Calculations of UV/VIS spectrophotometer
UV/VIS spectrophotometer
Model: _____________________________                             Date: _________________
OBSERVATIONS:
Thickness of cell:

Spectral range:
240-300nm
Maxima absorption wavelength:
258nm, 264nm and 272nm
Sample:

Other reagent used:


No. of obs.
Concentration
Wavelength
Absorbance









CALCULATIONS:
Absorbance ratio at A264/A258 =
Absorbance ratio at A272/A258 =



Results: _______________
Remarks: ______________________________________________________________

                                                   



Annexure: 3
Observations of Optical rotation
Determination of Optical rotation
Instrument: ___________________                                              Date: _______________
Model: _______________________        Length of Polarimeter tube: ________________
Sample: ________________________________g.
Solvent: ________________________________ml.
Concentration of sample solution: ____________g/ml.
Blank solution:
Sr.#
Blank solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of blank solution: _______________
Sample solution:
Sr.#
Sample solution
Temperature
Optical rotation
(α)












                                                                                                 Average: _______________
Optical rotation of sample solution: ______________
Optical rotation of substance = Blank solution - Sample solution.



                                                                      Result: ________________
Remarks: ___________________________________________________________



Annexure: 4
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: 5
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
QCA
Quality control active ingredient
F
Format
Q.C
Quality control
Vol
Volume
%
Percentage
B.P
British pharmacopoeia
g
Grams
ml
Milliliter
oC
Degree centigrade
mg
Milligram
g
Grams
nm
Nanometer
M
Molar
h
Hour
vi
Initial volume
vf
Final volume
Ti
Initial temperature
Tf
Final temperature
Temp.
Temperature
UV/VIS
Ultraviolet/ visible
o
Degree (angle)
l
Length
c
Concentration (g/ml)
g/ml
Gram per milliliter
α
Alpha
λ
Lambda
g/L
Grams per liter
kPa
Kilo pascal


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