Quality control tests for Emulsions

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Quality control tests for Emulsions
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Emulsion

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

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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

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1. Determination of particle size and particle
count - It is performed by optical microscopy
and Coulter counter apparatus. 2. 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.
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Quality control tests for Emulsions- In case of
o/w emulsions, flocculation of globules causes an
immediate increase in viscosity. After this
change, the consistency ofthe emulsion changes
with time.- In case of w/o emulsions, the
dispersed phase particles flocculate quite
rapidly resulting in a decrease in viscosity,
which stabilizesafter 5 to 15 days.- As a
rule, a decrease in viscosity with age reflects
an increase of particle size due to coalescence.
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3. Determination of phase separation- Phase
separation may be observed visually or by
measuring the volume of the separated phases.4.
Determination of electrophoretic properties-
Determination of electrophoretic properties like
zeta potential isuseful for assessing
flocculation since electrical charges on
particles influence the rate of flocculation.-
O/W emulsion having a fine particle size will
exhibit low resistance but if the particle size
increase, then it indicates a sign of oil droplet
aggregation and instability.
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Assessment of emulsion shelf lifeThe final
acceptance of an emulsion depends on stability,
appearance, and functionality of the packaged
product. Stress conditions employed for
evaluating the stability of emulsions1- 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.- Cycling between two temperatures
(4 and 45C)- 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. In addition, the formulation of ice
crystals develops pressure that can deform the
spherical shape of emulsion droplets.
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2- 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. ? Centrifugation at 3750 rpm
for 5 hours effect of gravity for one year.?
No serious deterioration at 2000-3000 rpm at room
temperature.? Ultracentrifugation of emulsions
creates three layers a top layer of coagulated
oil, an intermediate layer of un-coagulated
emulsion, and an essentially pure aqueous layer.
The force of ultracentrifugation does not cause
oil separation until it is high enough to break
or rupture the absorbed layer of emulsifier that
surrounds each droplet.
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a centrifuged emulsion with surfactant sediment
(a),aqueous layer (b),emulsion layer
(c),close-packed oil droplets (d).
Overview of the possible effects during emulsion
centrifugation for O/W and W/O emulsions(a)
flocculation (b), coalescence(c), fractionation
according to particle size distribution(d),
detection of the presence of a surfactant
aggregate(e) (promoting emulsion creaming by the
depletion effect)
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3- Agitation? Simple mechanical agitation can
contribute to the energy with which two droplets
impinge upon each other. It is rarely appreciated
how useful the evaluation of an emulsion by
agitation at or near room temperature can be.?
It was already noted that excessive shaking of an
emulsion or excessive homogenization may
interfere with the formation of an emulsions.
Agitation can also break emulsions. A typical
case, is the manufacture of butter from milk.
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Quality control of suspension

• ? A pharmaceutical suspension is a coarse
  dispersion in which internal phase is dispersed
  uniformly throughout the external phase.
• ? The internal phase consisting of insoluble
  solid particles which is maintained uniformly
  throughout the suspending vehicle with aid of
  single or combination of suspending agents.
• ? The external phase (suspending medium) is
  generally aqueous in some instance, may be an
  organic or oily liquid for non oral use..

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Features Desired In PharmaceuticalSuspensions
1. The suspended particles should not settle
rapidly and sediment produced, must be easily
re-suspended by the use of moderate amount of
shaking. 2. It should be easy to pour yet not
watery and no grittiness. 3. It should have
pleasing odour, colour and palatability. 4. It
should be physically, chemically and
microbiologically stable. 5. Parenteral/Ophthalmi
c suspension should be sterilizable.
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The following tests are carried out in the final
quality control of suspension
? Appearance Color, odor and taste ?
Sedimentation volume ? Rheological measurement ?
Zeta Potential measurement ? Physical
characteristics such as particle size
determination ? pH
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Evaluation of suspensions
Suspensions are evaluated by determining their
physical stability.Two useful parameters for the
evaluation of suspensions are A- sedimentation
volumeB- degree of flocculation - The
determination of sedimentation volume provides a
qualitative means of evaluation.- A quantitative
knowledge is obtained by determining the degree
of flocculation.
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Sedimentation volume

• ? Since redispersibility is one of the major
  considerations in assessing the acceptability of
  a suspension, and since the sediment formed
  should be easily dispersed by moderate shaking to
  yield a homogenous system, measurement of the
  sedimentation volume and its ease of redispersion
  from two of the most common basic evaluative
  procedures.
• ? The concept of sedimentation volume is simple.
  It considers the ratio of the ultimate or final
  height of sediment (Hu) to the initial or
  original height (Ho) of the total suspension
  before settling as the suspension settles in a
  cylinder under standard conditions. The larger
  this fraction, the better is the suspendability.
• F Hu/Ho or Vu/Vo

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F has values ranging from less than one to
greater than one. normally F lt 1When F lt 1 ?
Vu lt VoWhen F 1 ? Vu VoThe system is in
flocculated equilibrium and show no clear
supernatant on standing.When F gt 1 ? Vu gt
VoSediment volume is greater than the original
volume dueto the network of flocs formed in the
suspension and soloose and fluffy sediment
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Sedimentation volume
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Degree of flocculation (ß)
It is a very useful parameter for flocculation
? In flocculated suspension, formed flocks (loose
aggregates). flocculated suspensions sediment
more rapidly. The volume of final sediment is
thus relatively large and is easily redispersed
by agitation. ?In deflocculated suspension,
individual particles are settling, so rate of
sedimentation is slow which prevents entrapping
of liquid medium which makes it difficult to
re-disperse by agitation. This phenomenon also
called cracking or claying.
Sedimentation behaviour of flocculated and
deflocculated suspensions
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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.
• ? So as 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.
• ? Thus, the viscosity of suspension should be
  maintained within optimum range to yield stable
  and easily pourable suspensions.

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• ? A practical rheologic method involves the use
  of Brookfield viscometer mounted on a helipath
  stand. The T-bar spindle is made to descend
  slowly into the suspension, and the dial reading
  on the viscometer is then measure of the
  resistance the spindle meets at various levels in
  a sediment.
• ? Data obtained on samples variously aged and
  stored indicate whether undesired changes are
  taking place. This measurement is made on
  undisturbed samples of different ages. The
  results indicate how the particles are settling
  with time.
• ? In screening study, the better suspensions show
  a lesser rate of dial reading with spindle turns,
  i.e., the curve is horizontal for a longer
  period.

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Electrokinetic techniques

• ? An electrophoretic method that employed a
  micro-electrophoresis apparatus.
• ? 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 , zeta potential was again
  determined by microscope electrophoresis. It was
  found that certain zeta potentials produced more
  stable suspensions because aggregation was
  controlled and optimized.

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Particle size changes

• ? It used for stability testing purposes.
• ? Particle size distributions are sometimes
  determined by microscopic means. This method of
  necessity requires dilute suspensions that are
  counted with the aid of an ocular grid.

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Packaging and Storage of Suspensions
1) Should be packaged in wide mouth containers
having adequate air space above the liquid. 2)
Should be stored in tight containers protected
from freezing. excessive heat light. 3)
Label "Shake Before Use" to ensure uniform
distribution of solid particles and thereby
uniform and proper dosage.
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