MISCELLANEOUS

DETERMINATION &
TESTS
By : Dr. Shumaila Shafique
 Contents

• Determine weight / ml
• Determine water / Moisture content
• Toxicity tests & identification tests
• Evaluate ointment
• Evaluate Ash contents
• Alkalinity of glass
 Lecture 1(22-09-16)
Learning objectives
At the end of this lecture students will be able
to
• Define weight per milliliter.
• Analyze the importance of wt/ml.
• Interpret the methods used to determine
water/moisture contents in drug.
• Discuss the importance these methods.
Weight /milliliter
• weight /ml of a liquid
“ is the weight in gm of 1ml of a liquid at 200C in
air .”
Temperature Weight of a liter of
water in g
200C 997.18

250C 996.02

300C 994.62
Determined by

Weight/ml =
The weight in air, of the quantity of liquid that fills a pycnometer at the specified temperature
(gm)
The capacity, expressed in (ml), of the pycnometer at the same temperature.

The “capacity of the pycnometer is ascertained/established from the

weight in air, expressed in g, of the quantity of water required to fill the
pycnometer at that temperature.
 Application
• Liquids containing extractives such as tinctures and
extracts.
• In the assays in monographs for Oral solutions and Oral
suspensions.
The quantity of the oral solution or suspension taken for
assay purposes is weighed accurately and the weight
per ml determined in order to calculate the content as
weight in volume (g per ml).
Water/moisture content
“The quantity of water contained in a material”.

• Method I (Titrimetric),
• Method II (Azeotropic), or
• Method III (Gravimetric)
under the heading Water, when water of hydration contained in an
article
• The heading Loss on Drying
in those cases where the loss sustained on heating may be not entirely
water but other volatile matter.
1. Gravimetric (drugs containing no constituents
other than water)
2. Gravimetric (drugs containing ether-soluble
constituents volatile at 1050C)
3. Azeotropic
4. Karl Fischer (Titrimetric)
5. Dew point
6. Hygrometric
7. Psychrometric
• Gravimetric analysis
“ Technique use for the quantitative determination
of an analyte based on the mass of a solid.”

This method determine the loss due to water or

volatile matter on drying by weight difference.
10 gm drug
1050C for 5 hrs
Dried & Re-weigh sample

For 1 hr
Repeated Drying
Limit :
difference b/t two weighing NMT 0.25%
 Azeotropic method
• The word azeotrope is derived from the Greek
words meaning, "no change on boiling".
• Grind samples containing coarse particles
• Dry distilling flask overnight in an air oven at 100 °C.
• Weigh accurately about 30g of sample and transfer to the
distilling flask expected to yield 2–4 mL of water.
• Add approx. 200mL of toluene and place the flask and its
contents on the hot plate-stirrer.
• Avoids splashing sample suspension on distilling flask walls.
• Apply heat(15min) so that distillation occurs at a rate
providing about 2 drops of condensate per second to fall
from the condenser tip.
• After 1 hour, increase distillation rate to give about 4drops/
sec.
• Continue the distillation until the volume of water
ceases (8hrs usually sufficient).
• Wash down the condenser with about 10mL of
toluene, continue the distillation for 30 minutes.
• Discontinue and Read the volume of water
• Determine a blank by the above procedure
substituting about 3 g of water,
• Weighed accurately, for the sample.
% Moisture= (Water in Trap, mL + Blank, mL)×100
Sample Wt. (g)

Blank = Water added (g) – Water Recovered (mL)

 Lecture 2
27-9-16
At the end of this lecture students will be
able to
• Define loss on drying.
• Explain the procedure to apply for this
test.
• Procedure and importance of Karl Fischer
titration.
 Loss on Drying

• Application : designed to measure the amount of

water or volatile matter in a sample under specified
condition.

• Procedure: Weigh the substance (1 to 2 g).

• Conditions : For large sized crystals sample, reduce
the particle to about 2 mm by quickly crushing.
 Procedure

• Tare a glass-stoppered, shallow weighing bottle that

has been dried for 30 minutes.
• Put the test specimen in the bottle, replace the cover,
and accurately weigh the bottle and the contents.
• Distribute by shaking test specimen.
• Place the bottle in drying chamber, removing the
stopper and leaving it also in the chamber.
 contd

• For temperature and time see monograph.

• [NOTE—The temperature specified in the
monograph is within the range of ± 2°C of the stated
figure]
• Open the chamber, close the bottle promptly, and
cool to room temperature in a desiccator before
weighing.
• Drying shall be continued until two consecutive
weighing do not differ by more than 0.50 mg per g of
substance.
 LOD (BP 2008)

• Expressed as loss of weight in w/w%

• Method:
Place a prescribed quantity of sample in a dried bottle.
• If the range of temp for drying is not given then follow
the single value ± 2°C.
• Dry the substance to constant mass or for prescribed
time by any one method
 Drying Methods
1.“In a desiccator”: the drying is carried out over
diphosphorous pentoxide at atmospheric pressure and
at RT (relative temperature).

2. “In vacuo”: the drying is carried out over

diphosphorous pent oxide at a pressure of 1.5kPa to
2.5kPa
3. If the substance melts at a lower temperature than that
specified, use 5-10°C below the melting temp. then dry.
4. Where capsules are to be tested take powder from 4
capsules.
5. Where tablets are to be tested take 4 tablets.
 Karl-Fischer Titration

• Widely used analytical method for quantifying water

content in a variety of products.

• Principle
based on the Busen reaction between iodine and
sulfur dioxide in an aqueous medium.
• Reagent contains;
a primary alcohol (methanol) as the solvent, and a base
(pyridine) as the buffering agent, iodine and sulphur
dioxide.
 How does it work?
• Water and iodine are consumed in a 1:1 ratio in the
reaction.
• Once all of the water present is consumed, the presence
of excess iodine is detected voltametrically by the
titrator’s indicator electrode. That signals the end-point
of the titration and by color change.
• The amount of water present in the sample is calculated
based on the concentration of iodine in the Karl Fischer
titrating reagent (i.e., titer) and the amount of Karl
Fischer reagent consumed in the titration.
Karl-Fischer titrator
 Dew point
Dew points indicate the amount moisture in the air.
• An excellent moisture content measuring option when
both water content and water activity measurements are
needed on the same sample.

• The accuracy cannot be assessed because there is, to

date, no absolute method for measuring moisture
content
 Nine products, representing a wide variety of types, from homogeneous ingredients to
complex final products, were selected for testing. The products included milk powder, flour,
dry dog food, chocolate syrup, granola bars, potato flakes, solid dosage tablets, whole wheat, and beef
jerky.
 Hygrometric Method
• By using hygrometer
• Used for environmental moisture content
monitoring
 Psychromatric method
• By using psychrometer:
• Mainly used for environmental moisture
content monitoring