1.0 OBJECTIVE:
To
lay down a procedure for the active raw material of the Calcium carbonate 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
(1 test tubes, 1 spatula, 1 pipette).
5.1.2.1.2
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
a test tube and add small quantity of sample for testing solubility according
to B.P specifications.
5.1.2.3.2
Add
purified water in it and observe.
5.1.2.4 Observations:
5.1.2.4.1
The
sample in test tube containing with water is practically insoluble.
5.2 Solution
S:
5.2.1
Material
and equipment:
5.2.1.1 Glassware (1 100.0ml of beaker, 1 spatula,
1 glass rod, 1 pipette).
5.2.1.2 Dilute acetic acid.
5.2.1.3 Water-bath.
5.2.1.4 Analytical weighing balance.
5.2.1.5 Magnetic stirrer.
5.2.2
Sample:
5.2.2.1 5.0g.
5.2.3
Preparation
of solution S:
5.2.3.1 Take a beaker of 100.0ml and add sample 5.0g
in it.
5.2.3.2 Add in it 80.0ml of dilute acetic acid.
5.2.3.3 Dissolve it by using magnetic stirrer
operate.
5.2.3.4 When the effervescence ceases, boil for
2min on water-bath.
5.2.3.5 Allow it to cool.
5.2.3.6 Dilute it to 100.0ml with dilute acetic
acid.
5.2.3.7 Filter it by using filtration apparatus,
if necessary, through the sintered-glass filter.
5.3 Identification
tests:
5.3.1
Carbonates test:
5.3.1.1 Material and equipment:
5.3.1.1.1
Glassware
(test tubes, beakers, spatula, stirrer & stoppers of test tube).
5.3.1.1.2
Magnetic
stirrer.
5.3.1.1.3
3.0ml
of 2M acetic acid.
5.3.1.1.4
5.0ml
of 0.1M barium hydroxide.
5.3.1.1.5
Excess
of 7M hydrochloric acid.
5.3.1.1.6
Magnesium
sulfate.
5.3.1.1.7
Purified
water (q.s).
Test no.
|
Sample
|
Method
|
Observation
|
1.
|
0.1g
|
Take
a test tube and add 0.1g of sample in it. Dissolve in 2.0ml of purified
water.
Add
3.0ml of 2M acetic acid in another test tube.
Close
the test tube immediately using a stopper fitted with a glass tube bent at two
right angles.
The
solution or suspension produces effervesce evolving a colourless and odorless
gas.
Heat
it gently on burner & collect gas in 5.0ml of 0.1M barium hydroxide,
which is in another test tube taken.
Observe
change in colour and appearance of solution after addition of an excess of 7M
hydrochloric acid.
|
A
white ppt is produced which dissolves on addition of an excess of 7M
hydrochloric acid.
|
2.
|
Solution
S
|
Take
a test tube and add solution S in it.
Add
in it solution of magnesium sulfate.
Observe
changes.
|
A
white ppt is produced (distinction from bicarbonates).
|
5.3.2
Calcium test:
5.3.2.1 Material and equipment:
5.3.2.1.1
Glassware
(according to requirement).
5.3.2.1.2
0.5ml
of a 2.0g/L solution of glyoxal-hydroxyanil in ethanol (96%).
5.3.2.1.3
0.2ml
of dilute sodium hydroxide solution.
5.3.2.1.4
0.2ml
of sodium carbonate solution.
5.3.2.1.5
Chloroform
(1-2ml).
5.3.2.1.6
Purified
water.
5.3.2.2 Sample:
5.3.2.2.1
0.2ml
of solution S.
5.3.2.3 Method of analysis:
5.3.2.3.1
Take
a test tube and add 0.2ml of solution S.
5.3.2.3.2
Add
0.5ml of a 2.0g/L solution of glyoxal-hydroxyanil in ethanol (96%), 0.2ml of
dilute sodium hydroxide solution, 0.2ml of sodium carbonate solution.
5.3.2.3.3
Shake
it well with 1-2ml of chloroform.
5.3.2.3.4
And
add 1-2ml of purified water.
5.3.2.3.5
Observe
the colour change.
5.3.2.4 Observations:
5.3.2.4.1
The
chloroform layer is colored red.
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. Operate it
according to the SOP.
5.4.3.3 Place the sample into the tray and dry it.
5.4.3.4 Set the temperature of oven at 200±10oC
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. Operate analytical
weighing balance according.
5.4.3.7 Note down readings on given Annexure-1
5.4.4
Observation:
5.4.4.1 Maximum 2.0%.
5.5 Assay:
5.5.1
Apparatus:
5.5.1.1 Glassware (1 100.0ml of beaker, 1 50.0ml
of beaker, 1 spatula, 1 glass rod, 1 pipette).
5.5.1.2 Analytical weighing balance.
5.5.1.3 Water bath.
5.5.1.4 Magnetic stirrer.
5.5.1.5 Titration apparatus.
5.5.2
Material and reagents:
5.5.2.1 0.1M sodium edetate.
5.5.2.2 3.0ml of dilute hydrochloric acid.
5.5.2.3 6.0ml of strong sodium hydroxide.
5.5.2.4 200mg of calconecarboxylic acid triturate
(as indicator).
5.5.2.5 Purified water (q.s).
5.5.3
Sample:
5.5.3.1 0.150g
5.5.4
Method of analysis:
5.5.4.1 Take a 100.0ml of beaker and add 0.150g of
sample in it.
5.5.4.2 Add mixture of 3.0ml of dilute
hydrochloric acid and 20.0ml of purified water in it, dissolve by using glass
rod and heat on water-bath until boil for 2min.
5.5.4.3 Allow it to cool and dilute it to 50.0ml
with purified water.
5.5.4.4 Take a conical flask of 500.0ml and add
above prepared solution.
5.5.4.5 And dilute it to 300.0ml with purified
water.
5.5.4.6 Add 6.0ml of strong sodium hydroxide and
about 200mg of calconecarboxylic acid triturate (as indicator).
5.5.4.7 Set titration apparatus.
5.5.4.8 Titrate with 0.1M sodium edetate until the
colour changes from violet to full blue.
5.5.4.9 The above procedure is for sample
titration and similarly performs the blank titration without using sample.
5.5.4.10 Note down the volume used as shown in
Annexure-2.
5.5.4.11 Take 3 readings at least and take average
for both sample titration and blank titration.
5.5.4.12 Calculate percentage purity.
5.5.4.13
Calculations:
5.5.4.13.1 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.
5.5.4.13.2 For percentage purity use formula:
%age purity = volume
used by substance x factor x 100
Weight of sample
5.5.4.13.3 Put values and calculate %age purity.
5.5.5
Factor:
5.5.5.1 1ml of 0.1M sodium edetate is equivalent
to 10.01mg of CaCO3.
5.5.6
Limit:
5.5.6.1 98.5% to 100.5% (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 /Calcium
carbonate: 2015, pp. 364-365.
7.2 The British Pharmacopoeia. Vol V., Official Monograph /Qualitative
Reactions and Tests: 2015, pp. 266-270.
7.3 The British Pharmacopoeia. Vol V., Official Monograph /Complexometric
Titration: 2015, pp. 281-282.
8.0 ANNEXURES:
Annexure 1:
Observations of Percentage Loss of drying by using oven.
Annexure 2: Observations
and calculations of assay of calcium carbonate.
Annexure: 1
Observations
of percentage loss of drying by using Oven
Percentage loss
of drying by using Oven
Weight
of Sample = _____________
Time
period = _____________
Pressure=
_________________
Average
% Loss of Moisture: _____________
Remarks: _______________________________________________________________
|
||||||||||||||||||||||||
Annexure:
2
Observations
and calculations of assay of calcium carbonate.
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
|
Sr.#
|
Serial
number
|
Q.C
|
Quality
control
|
%
|
Percentage
|
B.P
|
British
pharmacopoeia
|
g
|
Grams
|
ml
|
Milliliter
|
Min
|
Minutes
|
ppt
|
Precipitates
|
oC
|
Degree
centigrade
|
mg
|
Milligram
|
M
|
Molar
|
Vol
|
Volume
|
vi
|
Initial
volume
|
vf
|
Final
volume
|
QCA
|
Quality
control active ingredient
|
F
|
Format
|
g/L
|
Gran
per liter
|
R
|
Reagent
|