Quality control of parentral

products, suspensions and emulsons

Quality control of parentral products

Quality control of parentral products
Injections are sterile, pyrogen free preparations
intended to be administered parenterally (outside
alimentary tract).
All parenterals, as well as nasal, ophthalmic
solutions, must be sterile, including packaging
materials.
Containers for parenteral preparations are made as far
as possible from materials that are sufficiently
transparent to permit the visual inspection of the
contents, except for implants

 Parenteral preparations are supplied in

glass containers or in other containers such
as plastic containers and prefilled syringes.
The tightness of the container is ensured by
suitable means. Closures ensure a good
seal, prevent the access of microorganisms
and other contaminants and usually permit
the
withdrawal of a part or the whole of the
contents without removal of the closure.

 Contamination:

Chemical composition
pH
Sterility (e.g.microorganism contamination)
Pyrogenicity
Physical appearance
Particulate matter (e.g. dust, glass or precipitation)

Sources of product contamination

Touch contamination
Generation of particulates from shedding cells or hair
Air Supply
Heating, Ventilation and Air Conditioning (HVAC)
Infiltration
Particles from adjacent spaces (e.g. entrance, hall)
Internal generation
Walls, floors, ceilings, packaging, equipment

 Necessities of Parenteral preparations:

Sterility (must)
Free from Pyrogen (must)
Free from particulate matter (must)
Clarity (must)
Stability (must)
Isotonicity (should)
Solvents or vehicles used must meet special purity and other
standards.
Restrictions on buffers, stabilizers, antimicrobial preservative.
Do not use coloring agents.
Must be prepared under aseptic conditions.
Specific and high quality packaging.

 Parenteral products require additional tests, which

include those of sterility, pyrogen, clarity, and
particulate analysis, and for glass-sealed ampoules,
leaker test.
1.Volume in container
The total fluid volume that must be filled into a unit
parenteralcontainer is typically greater than the
volume that would contain the exact labeled dose.

 2. Clarity testing and particulate analysis:

a. Clarity examination
b. Particulate matter

3. Pyrogen test: Pyrogenic substances are

primarily lipid polysaccharide products of the
metabolism of microorganisms, they may be soluble,
insoluble or colloidal.

 Pyrogen produced by gram-negative bacilli are

generally the most potent. Minute amounts of
pyrogens produce a wide variety of reactions
in both animals and humans, including fever,
leukopenia and i.e alteration in blood coagulation.
One pyrogen test is a qualitative biological test based
on the fever response of rabbits. The test aims of
measuring the rise in body temperature in healthy
rabbits by the intravenous injection of a sterile
solution of the substance under test.

Sources of pyrogen contamination

- Solvent-possibly the most important source.
- The medicament
- The apparatus
- The method of storage between preparation and
sterilization

Rabbit pyrogen test

Rabbits must be healthy and mature
Either sex may be used
Must be individually housed between 20 and 23C
Weighing not less than 1.5 kg
Fed a complete and balanced diet not containing
antibiotics,
and not showing loss of body mass during the week
preceding
the test.

 Limulus Amoebocyte Lysate (LAL) test.

This test is more sensitive, more
rapid, and easier to perform than the
rabbit test.

Quality control tests for Emulsions

An emulsion is a biphasic liquid penetration
containing two immiscible liquids, one of
which is dispersed as minute globules into the
other.

 Evaluation tests for emulsion

Average globular size and size distribution
Number of globules
Rheological evaluation
Zeta potential
In vitro drug release
In vitro stability study

 Determination of particle size and particle count:

-It is performed by optical microscopy and Coulter
Counter
Determination of viscosity:
-Determination of viscosity is done to assess the
changes that might take place during aging.

 The viscometers used: cone and plate viscometers.

In case of o/w emulsions, flocculation of globules
causes an immediate increase in viscosity. After this
change, the consistency of the emulsion changes with
time.

In case of w/o emulsions, the dispersed phase

particles flocculate quite rapidly resulting in a
decrease in viscosity, which stabilizes after 5 to 15
days.

 As a rule, a decrease in viscosity with age reflects an

increase of particle size due to coalescence.
3. Determination of phase separation:
Phase separation may be observed visually or by
measuring the volume of the separated phases.

 Determination of electrophoretic properties:

Determination of electrophoretic properties like zeta
potential is useful for assessing flocculation since electrical
charges on particles influence the rate of flocculation.
Assessment of emulsion shelf life:

The final acceptance of an emulsion depends on

stability, appearance, and functionality of the packaged
product. Stress conditions employed for evaluating the
stability of emulsions:

1. Aging and temperature

It is routine to determine the shelf life of all types
of preparations by storing them for varying periods
of time at temperatures that are higher than those
normally encountered.
At elevated temperature: accelerates the rate of
coalescence and creaming and this is coupled with
change in viscosity. Most emulsions become thinner
at elevated temperature and thicken when allowed to
come to room temperature.

 Freezing damage emulsion more than heating

Since, the solubility of emulsifiers is more sensitive
to freezing than heating.
Centrifugation
It is accepted that shelf life under normal storage
conditions can be predicted rapidly by observing the
separation of the dispersed phase due to either
creaming or coalescence when emulsion is exposed to
centrifugation.

Quality control of suspension

A pharmaceutical suspension is a coarse dispersion in
which internal phase is dispersed uniformly
throughout the external phase.
Rheologic methods: Viscosity of suspensions is of
great importance for stability and pourability of
suspensions. As we know suspensions have least
physical stability amongst all dosage forms due to
sedimentation and cake formation.

The viscosity of the dispersion medium increases, the

terminal settling velocity decreases thus the dispersed
phase settle at a slower rate and they remain
dispersed for longer time yielding higher stability to
the suspension.
On the other hand as the viscosity of the suspension
increases, its pourability decreases and
inconvenience to the patients for dosing increases.
A practical rheological method involves the use of
Brookfield viscometer

 Electrokinetic techniques
Such instrumentation permitted measurement of the
migration velocity of the particles with respect to the
surface electric charge or the familiar zeta potential.
The evaluation of suspensions by electrokinetic methods
showed that the zeta potential changes upon the addition
of additives and is related to stability.
The zeta potential was correlated to visually observed
caking

 Particle size changes

It used for stability testing purposes
Packaging and Storage of Suspensions:
Should be packaged in wide mouth containers having
adequate air space above the liquid.
Should be stored in tight containers protected from:
freezing.
excessive heat & light.
Label: "Shake Before Use" to ensure uniform
distribution of solid particles and thereby uniform and
proper dosage.