Miscellaneous

Determinations and Tests

Lecture 07
Detremination of Weight per ML
Weight per ML

“The weight per milliliter of a liquid is the weight expressed

in grams of 1 milliliter of a liquid when weighed in air at the
specific temperature”

According to BP; it is weight in g of 1ml of a liquid when

weighed in air at 20 degrees, unless otherwise specified In
the monograph.
• This method is used, where indicated, 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. The weight per ml is
determined to calculate the content as weight in volume
(g per mL).
Weight per ML Almost equal to density of the
liquid, For this,
Weigh a clean and dry
pycnometer
accurately

Fill it with liquid, remove

any access and weigh

Determine the weight of liquid by

subtraction
Weight per ml = W2 – W1
V
DENSITY

A material's density is defined as its mass per unit volume.

It is, essentially, a measurement of how tightly matter is crammed together.
The principle of density was discovered by the Greek scientist Archimedes .
To calculate the density of an object, take the mass ( m ) and divide by the
volume ( v ). This will give you the density in g/cm3 .
•A ship floating on water is a great
illustration of the difference between
mass and density.
•A ship must have a density of less
than 1.0 g/cm3 (the density of water),
or it will sink.
•Ships have a large mass, because
they are made of steel, but because
they have a large volume, their
density is less than 1.0 g/cm3. If
enough mass is added to them such
that their density goes above 1.0
g/cm 3 , they will sink.
Loss on Drying

To measure the amount

of water and volatile
matters

Sample is dried under

specified conditions.
 USP Procedure
1. Take 1-2g of substance, reduce particle size if necessary, in a dried glass
stoppered, weighed bottle

2. Weigh and shake to evenly distribute the substance.

3. Place the loaded bottle in drying chamber, remove stopper and place it
also in the chamber.

4. Dry the sample at temperature specified in monograph, close the bottle.

Cool in desiccator & weigh
If “dry to constant weight”, until two consecutive
weighings do not differ by more than 0.50 mg per g of
substance

Where capsules are to be tested, use a portion of the

mixed contents of not fewer than 4 capsules.

Where tablets are to be tested, use powder from not

fewer than 4 tablets
If the substance melts at a temperature at which loss
on drying is to be performed, it is kept at 5 -10oC for
1-2 h for drying.

For substance requiring thermogravimetric

analysis a sensitive electrobalance is used.

For vacuum drying vacuum desiccator or

vacuum drying pistol are used.
Digital moistur analyzer
Determination of Moisture Content
Moisture Content

a) Heating method
thermogravimetry

b) Karl Fischer
Volumetric method
Coulometric method
Heating Method

• Accurately weighed powder (2 g) of the plant material is

taken in a tarred silica crucible.

• The powder is the dried in an oven at 105oC for 30 min,

cooled at room temperature in a desiccator until constant
weight and weighed to calculate the moisture contents.

• The results are expressed as a percent of dry powder.

Karl Fisher Method---Standard technique for low
moisture products.

Especially useful for reducing sugars, protein-rich

food and foods and pharmaceuticals with high
volatile oils.
Karl Fischer was a German
chemist. In 1935 he published a
method to determine trace
amounts of water in samples.
This method is now called Karl
Fischer titration and was
originally performed manually
but has been automated.

Bunsen Reaction
2 H2O + SO2+ I2 = H2SO4 + 2 HI
KARL FISCHER TITRATION PRINCIPLE

The Karl Fischer Titration is based on an iodine / iodide reaction:

• The water reacts with iodine. The endpoint of the titration is reached when
all the water is consumed. a sulfate compound
• The process uses an organic base (B), sulphur dioxide, iodine and an alcohol.
• The original Karl Fischer method used pyridine as organic base and methanol
as alcohol.
• Since then the reagents have been improved. Nowadays Karl Fischer reagents
are available which are less toxic (no more pyridine but imidazole as organic
base, ethanol instead of methanol) and which provide a faster reaction.
• During the titration, iodine is added to sample and the amount of iodine used
to consume all the water contained in the sample is measured.
Volumetric Karl Fischer Titration:
• a solution with an exactly known concentration of iodine is added to
the sample by means of an electric burette. The amount of iodine
added to the sample is calculated from the volume of the iodine
solution used.

Coulometric Karl Fischer Titration:

• The iodine is electrolytically generated. The amount of iodine added
to the sample is determined by measuring the current needed for the
electrochemical generation of the iodine. When reacting with water,
the brown iodine is reduced to the colorless iodide.

Hybrid Karl Fischer titration:

• Is basically a combination of both, the coulometric and the volumetric
method: The iodine is electrolytically generated and –if the moisture
content of the sample exceeds a certain level – a solution with an
exactly known concentration of iodine is added at the same time.
1. Physical Appearance

• Cracking of creams (separation

of oil and water)
The main • Development of granular and
characteristics lumpy appearance
need to be • Marked change in viscosity
checked are • Crystal growth
• Microbial contamination
2. Particle Size Determination
• Dilute a suitable quantity of preparation with equal
volume of glycerol or liquid paraffin, as specified

• Mount on a glass slide and examine under light

microscope

• Count the number of particles with daimeter above or

below than that specified in monograph

• Compare the percentage with official limits

3. Weight Wariation Test

• Applies to those products in which labeled net weight

is not more than 150g

• Select 10 filled containers, remove the label, clean

and weigh individually

• Remove the contents by cutting the containers

and wash with suitable solvent
• Dry and again weigh each empty container together with
its corresponding part, take difference as weight of
contents.

• The average net weight of contents of 10 containers

should not be less than the labeled amount

• The net weight of contents of any single container

should not be less than 90% of the labeled amount (for
≤ 60g)
• And not less than 95% of the labeled amount (60-150g)

• If this requirement is not met repeat this procedures taking

additional 20 containers

• The average net weight of contents of 30 containers should

not be less than labeled amount

• Contents of not more than 1 of the 30 units should be less

than 90% of the stated amount (for ≤ 60g)

• And not less than 95% of the labeled amount (60-150g)

4. Solubility Test

The The
preparation preparation
should be should be
soluble in 9 miscible with
parts of water alcohol, ether
and 1.7 parts and
of hot water chloroform
5. Viscosity Determination

• Viscosity is determined using a method specified in official

monograph.
• Instruments used to measure viscosity is called “rheometers” and
“viscometers”
6. Assay of Active Ingredient

Assay of active
ingredients Percentage
should be contents should
performed be within the
according to official limits
monograph
7. Microbial Contamination

• Microorganisms can grow, if no preservative is added,

or even if added, its efficiency is reduced due to
interaction with other ingredients

• Microorganisms may get into the preparation during

handling and storage

• Therefore, aseptic techniques of handling are

needed
Antimicrobial
assay • Direct inoculation
should be
performed method
according to
official • Membrane filtration
monograph, method
usually
8. Metal Particles in Opthalmic Ointment
• Extrude completely the contents of 10 containers separately into flat
bottom petri dishes

• Cover, heat at 85oC for 2 h and cool slowly to solidify

• Remove the cover and invert on the stage of microscope adjusted to

30 times magnification and equipped with eye-piece micrometer disk
calibrated for this magnification.

• Additional illuminator may also used

• Examine the entire bottom of Petri dish for metal particles.

• Count the metal particles of 50µm or larger

• The requirement is met if total number of such particles in all 10 tubes

does not exceed 50

• Not more than 1 tube contains more than 8 such particles

• If not, repeat with 20 more tubes

• The requirement is met if total number of such particles in 30 tubes is

not more than 150
• And not more than 3 containers allowed to contain more than 8
• particles