BETAHISTINE DIHYDROCHLORIDE B.P. SOP



BETAHISTINE DIHYDROCHLORIDE B.P. SOP

1.0  OBJECTIVE:
To lay down a procedure of analytical report for the active raw material of Betahistine Dihydrochloride 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 slightly yellow powder, very hygroscopic.
5.1.2        Solubility:
5.1.2.1  Material and equipment:
5.1.2.1.1        Glassware (3 test tubes, 1 spatula, 1 pipette).
5.1.2.1.2        Purified water.
5.1.2.1.3        Ethanol.
5.1.2.1.4        2-propanol.
5.1.2.2  Sample:
5.1.2.2.1        Small quantity.
5.1.2.3  Method:
5.1.2.3.1        Take 3 test tubes and add small quantity of sample for testing solubility according to B.P specifications.
5.1.2.3.2        Add purified water, ethanol and 2-propanol in each test tube separately in a small volume and observe the solubility of the sample.
5.1.2.4  Observations:
5.1.2.4.1        The sample in test tube 1 containing with water is very soluble.
5.1.2.4.2        The sample in test tube 2 containing with ethanol is soluble.
5.1.2.4.3        The sample in test tube 3 containing with 2-propanol is practically insoluble.
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 according to the SOP No. BM/QCEO/SOP009-00.
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 Betahistine Dihydrochloride is 150oC to 154oC.
5.2.2        Chlorides test:
5.2.2.1  Material and equipment:
5.2.2.1.1        Glassware (according to requirement).
5.2.2.1.2        Dilute nitric acid.
5.2.2.1.3        0.4 ml of Silver nitrate R1.
5.2.2.1.4        Ammonia.
5.2.2.1.5         Purified water.
5.2.2.2  Sample:
5.2.2.2.1        Equivalent to 2.0mg of chloride
5.2.2.3  Method:
5.2.2.3.1        Take a test tube add in it 2.0ml of purified water with the help of pipette. And add a quantity of substance to be examined equivalent to about 2.0mg of chloride.
5.2.2.3.2        Acidify with dilute nitric acid.
5.2.2.3.3        And add 0.4ml of silver nitrate R1.
5.2.2.3.4        Shake and allow it to stand.
5.2.2.3.5        A curdled, white ppt. is formed.
5.2.2.3.6        Centrifuge it in centrifugation machine
5.2.2.3.7        The obtained ppt. is washed with 3 quantities, each of 1ml, of purified water.
5.2.2.3.8        Carry out this operation rapidly in subdued light, disregarding the fact that the supernatant solution may not become perfectly clear.
5.2.2.3.9        Suspend the precipitate in 2.0ml of water and add 1.5ml of ammonia.
5.2.2.3.10    Observe the changes.
5.2.2.4  Observations:
The precipitate dissolves easily with the possible exception of a few large particles which dissolves slowly.
5.3  Other tests:
5.3.1        Solution S:
5.3.1.1  Material and equipment:
5.3.1.1.1        Glassware (1 beaker, 1 stirrer, 1 spatula).
5.3.1.1.2        Carbon dioxide-free water.
5.3.1.2  Sample:
5.3.1.2.1         5.0g.
5.3.1.3  Preparation of Solution S:
5.3.1.3.1        Take a beaker of 50.0ml and add 5.0g of the sample in it.
5.3.1.3.2        Add sufficient quantity of carbon dioxide-free water and dissolve it by using stirrer.
5.3.1.3.3        Finally dilute it to 50.0ml with the same solvent.
5.3.2        pH:
5.3.2.1  Material and equipment:
5.3.2.1.1        Glassware (according to the requirement).
5.3.2.1.2        pH meter.
5.3.2.2  Sample:
5.3.2.2.1        Solution S.
5.3.2.3  Method:
5.3.2.3.1        Firstly clean the pH meter with clean dry cloth,
5.3.2.3.2        Operate the pH meter.
5.3.2.3.3        Rejuvenate the electrode before use according to SOP instructions, if there is any need of.
5.3.2.3.4        Calibrate the electrode of the pH meter.
5.3.2.3.5        Perform the test on solution S.
5.3.2.3.6        Take a beaker of 100.0ml and add solution S in it. Such that it immersed electrodes in it completely.
5.3.2.3.7        Maintain the temperature of sample at 25oC±2oC.
5.3.2.3.8        Dip the electrode along with temperature sensor into the sample.
5.3.2.3.9        When dipping electrode into sample, it must be completely immersed in it.
5.3.2.3.10    Stir the probe gently in the sample to create a homogeneous sample.
5.3.2.3.11    Allow the reading to stabilize for a time.
5.3.2.3.12    Record the observed values of pH & temperature in the respective Annexure-2.
5.3.2.3.13    Wash the electrodes again after use and store the electrode in storage solution.
5.3.2.3.14    Calibrate the instrument.
5.3.2.4  Observation:
5.3.2.4.1        2.0 to 3.0.
5.4  Loss on drying:
5.4.1        Material and equipment:
5.4.1.1  Glassware (according to requirement).
5.4.1.2  Analytical weighing balance.
5.4.1.3  Oven.
5.4.2        Sample:
5.4.2.1  1.0g.
5.4.3        Method:
5.4.3.1  Weigh 1.0g of the test sample.
5.4.3.2  Set the oven apparatus
5.4.3.3  Place the sample into the tray and dry it.
5.4.3.4  Set the temperature of oven at 105oC for at least 45 minutes.
5.4.3.5  And wait till the sample loses its moisture.
5.4.3.6  After 45 minutes weigh the sample again by using analytical weighing balance i.e. the final weight.
5.4.3.7  Note down readings on given Annexure-3.
5.4.4        Observation:
5.4.4.1  Maximum 1.0%.
5.5  Assay:
5.5.1        Apparatus:
5.5.1.1  Glassware (according to requirement).
5.5.1.2  Potentiometer.
5.5.2        Material and reagents:
5.5.2.1  50.0ml of ethanol.
5.5.2.2  0.1M sodium hydroxide.
5.5.2.3  Thymolphthalein solution as an indicator.
5.5.3        Sample:
5.5.3.1  80.0mg of sample.
5.5.4        Method of analysis:
5.5.4.1  Take a titration flask and add 80.0mg of sample in it.
5.5.4.2  Add 50.0ml of ethanol (96%) R and dissolve it by using magnetic stirrer
5.5.4.3  Fill the right hand side burette with titrant 0.1M sodium hydroxide
5.5.4.4  Carry out a Potentiometric titration using Thymolphthalein solution as an indicator.
5.5.4.5  Operate potentiometer.
5.5.4.6  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-4.
5.5.4.7  Plot a graph, volume used v/s millivolts.
5.5.4.8  Find out the END POINT.
5.5.4.9  Peak of graph indicates END POINT i.e. the point at which maximum millivolts. Note down volume used at that point.
5.5.4.10    Perform blank titration without using sample. Similarly, as sample titration performed. Record observations in annexure-4.
5.5.4.11    Calculate volume used by substance by using formula:
Volume used by substance = Blank titration - Sample titration.
5.5.4.12    Calculate percentage purity of the sample by using formula:
%age purity = volume used by substance x factor x 100
                          Weight of sample
5.5.5        Factor:
5.5.5.1  1ml of 0.1M Sodium hydroxide is equivalent to 10.46mg of Betahistine Dihydrochloride C8H14Cl2N2.
5.5.6        Limit:
5.5.6.1  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 /Betahistine Dihydrochloride: 2015, pp. 275-276.
8.0  ANNEXURES:
Annexure 1: Observations of Melting point apparatus.
Annexure 2: pH measurement.
Annexure 3: Observations of Percentage Loss of drying by using oven.
Annexure 4: 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
pH measurement

Sr.#
Temperature
pH

















Result: _________________________________________________________________















Annexure: 3
Observations of percentage loss of drying by using Oven

Percentage loss of drying by using Oven
Weight of Sample = _____________
Time period = _____________
Pressure= _________________
Sr.#
Time (min)
Weight of sample (g)
% Loss of Moisture
Initial weight
Final weight















Average % Loss of Moisture: _____________

% Loss of Moisture:








Remarks: _______________________________________________________________



Annexure: 4
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
oC
Centigrade
QCA
Quality control active ingredient
QCEO
Quality Control Equipment (Operation)
F
Format
Q.C
Quality control
mg
Milligrams
M
Molar
g
Grams
ml
Milliliter
v/s
Verses
%
Percentage
Sr.#
Serial number
B.P
British pharmacopoeia
mV
Millivolts
Vol.
Volume
oC
Centigrade


No comments:

Post a Comment