GUAIFENESIN SOP
1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Guaifenesin 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 crystalline powder.
5.1.2
Solubility:
5.1.2.1
Material and equipment:
5.1.2.1.1
Glassware (2 test
tubes, 1 spatula).
5.1.2.1.2
Alcohol.
5.1.2.1.3
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 2 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 alcohol in
test tube 2 and observe.
5.1.2.4
Observations:
5.1.2.4.1
The sample in test
tube 1 containing with purified water is sparingly soluble.
5.1.2.4.2
The sample in test
tube 2 containing with alcohol is soluble.
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 center 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 79oC-83oC.
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
Desiccator.
5.3.1.1.3
Diphosphorous
pentaoxide.
5.3.1.1.4
Analytical weighing
balance.
5.3.1.1.5
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.
5.3.1.3.2
Set the desiccator
apparatus with desiccant.
5.3.1.3.3
Place the sample
into the china dish or petri dish.
5.3.1.3.4
Set the temperature
60oC and at 1.5kPa to 2.5kPa pressure for at least 3h.
5.3.1.3.5
And wait till the
sample loses its moisture.
5.3.1.3.6
After 3h weigh the
sample again by using analytical weighing balance i.e. the final weight.
5.3.1.3.7
Note down readings
on given Annexure-2.
5.3.1.4
Observations:
5.3.1.4.1
Maximum 0.1%.
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
Reflux-condenser
apparatus.
5.4.1.4
Water-bath.
5.4.2
Material
and reagents:
5.4.2.1
Acetic anhydride.
5.4.2.2
Pyridine.
5.4.2.3
0.25ml of
phenolphthalein solution R (as indicator).
5.4.2.4
1.0M sodium hydroxide.
5.4.2.5
Purified water.
5.4.3
Sample:
5.4.3.1
0.5g.
5.4.4
Method
of analysis:
5.4.4.1 Sample
titration:
5.4.4.1.1
Take a beaker of
50.0ml and add 0.5g (m g) of sample
in it.
5.4.4.1.2
Add 10.0ml of a
freshly prepared mixture of 1 volume of acetic anhydride and 7 volumes of
pyridine.
5.4.4.1.3
Set the reflux
condenser apparatus.
5.4.4.1.4
Boil under a
reflux condenser for 45min.
5.4.4.1.5
Cool it and add
25.0ml of purified water.
5.4.4.1.6
Take a titration
flask and add sample solution approximate 10.0ml.
5.4.4.1.7
Set titration
apparatus.
5.4.4.1.8
Use 0.25ml of
phenolphthalein solution as indicator.
5.4.4.1.9
Titrate with 1.0M
sodium hydroxide (n1 ml).
5.4.4.1.10 Note
down the volume used as shown in Annexure-3.
5.4.4.1.11 Take
at least 3 readings and take average of it.
5.4.4.2 Blank
titration:
5.4.4.2.1
Take a beaker of
50.0ml and add 10.0ml of a freshly prepared mixture of 1 volume of acetic
anhydride and 7 volumes of pyridine.
5.4.4.2.2
Set the reflux
condenser apparatus.
5.4.4.2.3
Boil under a
reflux condenser for 45min.
5.4.4.2.4
Cool it and add
25.0ml of purified water.
5.4.4.2.5
Take a titration
flask and add sample solution approximate 10.0ml.
5.4.4.2.6
Set titration
apparatus.
5.4.4.2.7
Use 0.25ml of
phenolphthalein solution as indicator.
5.4.4.2.8
Titrate with 1.0M
sodium hydroxide (n2 ml).
5.4.4.2.9
Note down the
volume used as shown in Annexure-3.
5.4.4.2.10 Take
at least 3 readings and take average of it.
5.4.4.3 Calculate
percentage content of Guaifenesin C10H14O4
from the expression:
%age content of
Guaifenesin = 19.82 (n2-n1)
2m
5.4.5
Limit:
5.4.5.1 98.0%
to 102.0% (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 / Guaifenesin: 2015, pp. 1115-1116.
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
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 = _____________
Average % Loss of Moisture: _____________
Remarks:
____________________________________________________________
|
||||||||||||||||||||||||
Annexure:
3
Observations
and calculations of assay
Indicator:
___________________
Weight
of sample: ____________
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 content of Guaifenesin = 19.82
(n2-n1)
2m
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
|
|
g
|
Grams
|
|
ml
|
Milliliter
|
|
oC
|
Degree
centigrade
|
|
mg
|
Milligram
|
|
g
|
Grams
|
|
M
|
Molar
|
|
vi
|
Initial
volume
|
|
vf
|
Final
volume
|
|
Ti
|
Initial
temperature
|
|
Tf
|
Final
temperature
|