ReKm SUSPENSION
ReKm SUSPENSION
ReKm SUSPENSION
1 2
Suspension
Class Range of particle size Example
• A Pharmaceutical suspension is a coarse
dispersion in which internal phase
Molecular dispersion < 1 nm True solution (therapeutically active ingredient) is dispersed
Colloid dispersion 1 nm – 0.5 µm Colloidal Ag solution
uniformly throughout the external phase.
• The external phase (suspending medium) is
Coarse dispersion > 0.5 µm Suspension & emulsion
generally aqueous; in some instance, may be
an organic or oily liquid for non oral use.
3 4
Classification of suspensions
3.Based on Electrokinetic Nature of Solid
1. Based on General Classes
Particles
➢Oral suspension
➢Flocculated suspension
➢Externally applied suspension
➢Deflocculated suspension
➢Parenteral suspension
4. Based on Size of Solid Particles
2. Based On Proportion of Solid Particles
➢Coarse suspension (>1 micron)
➢Dilute suspension (2 to 10% w/v solid)
➢Colloidal suspension (< 1 micron)
➢Concentrated suspension (50% w/v solid)
➢Nano suspension (10 nm)
7 8
Theoretic consideration of suspensions
• Decrease in the rate of sedimentation of particles
A) Theory of sedimentation: Sedimentation in a suspension may be achieved by reducing the
means settling of particle or floccules occur under size of the dispersed particles and by increasing
gravitational force in liquid dosage form. the density and viscosity of the
dispersion/continuous phase.
Velocity of sedimentation expressed by Stoke’s Particle size of any suspension is critical, because-
equation ➢ Larger particles will settle faster at the bottom of
the container. The particle size can be reduced by
d2 (ρs − ρl )g using mortar and pestle.
Sedimentation rate =
18η ➢ But very fine particles will easily form hard cake
at the bottom of the container.
9 10
B) Zeta Potential
• Electrical double layer exists around each
particle which consists of two parts; an inner
region (Stern layer) where the ions are strongly
bound and an outer (diffuse layer) region
where they are less firmly associated. Within
this diffuse layer is a notional boundary within
which the particle acts as a single entity
(slipping or shear plane). The potential at this
boundary is the zeta potential.
11 12
• Zeta potential has practical application in stability of Deflocculated Suspensions
• In a deflocculated suspension, the dispersed particles remain
systems containing dispersed particles. This potential as discrete separated units and settling will be slow. The
governs the degree of repulsion between the supernatant of this suspension will continue to remain
adjacent, similarly charged, dispersed particles. cloudy for an appreciable time after shaking, due to the very
slow settling rate of the smallest particles in the product.
If the zeta potential is reduced below a certain value, • The slow rate of settling prevents the entrapment of liquid
within the sediment, which thus becomes compacted and
the attractive forces exceed the repulsive forces, and can be very difficult to redisperse. This phenomenon is
the particles come together. This phenomenon is called caking (or claying) and is the most serious of all the
known as flocculation. The flocculated suspension is physical stability problems encountered in suspension.
one in which zeta potential of particle is -20 to +20
• Deflocculated suspensions have the advantage of a slow
mV. sedimentation rate, thereby enabling a uniform dose to be
taken from the container.
13 14
Flocculated suspensions
• Formation of a loose aggregation of the particles held
together by weak Van der Waal's forces is termed a floc
or a floccule. The floccules have porous loose structure
and they can entrap a large amount of the liquid phase.
Therefore, the volume of the final sediment will still be
large and will easily be redispersed by moderate
agitation. Although flocs settle more rapidly than
individual discrete particles, flocculated particles
forming a type of lattice that resists complete settling
and thus are less prone to compaction and cake
formation than unflocculated particles.
Figure: a) deflocculated • In a flocculated suspension, the supernatant quickly
suspension and b) becomes clear, because of the large flocs that settle
flocculated suspension rapidly (inelegant appearance).
15 16
Formulation Components of suspensions
• Active pharmaceutical ingredient
• Vehicle (suspending medium)
Structured vehicle: Controlled flocculation: to
Flocculation in structured • Wetting agents
vehicle: the product can
to maintain the
deflocculated
produce flocs that, although, they
settle rapidly are easily look unsightly if the • Flocculating agent
particles in redispersed with a minimum of
agitation.
sedimentation volume (F)
is not close to or equal to
• Suspending agent
suspension
1. So a suspending agent • Buffers
is added to retard
sedimentation of the • Other additives (Osmotic Agents, flavour,
flocs. colour, preservatives, etc.)
17 18
19 20
• Contact angle: The angle, the liquid makes with the solid
surface is called contact angle. Contact angle can be used
to measure wettability. Generally, if the water contact
angle is smaller than 90°, the solid surface is
considered hydrophilic and if the water contact angle is
larger than 90°, the solid surface is
considered hydrophobic. To reduce the contact angle
between solid and liquid; the following agents can be
tried out:
A) Surfactants (HLB value 7-9): They reduce the interfacial
tension between the solid particles and a vehicle. As a
result of the lowered interfacial tension, contact angle is
lowered, air is displaced from the surface of the particles,
and wetting is promoted. E.g.: Non ionic surfactant
polysorbates.
• Disadvantage: they have foaming tendencies.
21 22
5. Suspending Agents
• Alginates
6. Buffers: To encounter stability problems all liquid
• Methylcellulose
formulation should be formulated to an optimum
• Hydroxyethylcellulose pH. Rheology, viscosity and other property are
• Carboxymethylcellulose dependent on the pH of the system. Most liquid
• Microcrystalline cellulose systems are stable at pH range of 4-10.
• Acacia • Most commonly used buffers are salts of week
• Tragacanth acids such as carbonates, citrates, gluconates,
• Xanthan gum phosphate and tartrates.
• Bentonite
• Carbomer • Na phosphate is most widely used buffer in
pharmaceutical suspension system. Citric acid is
Most suspending agents perform two functions i.e. besides acting most preferable used to stabilize pH of the
as a suspending agent they also imparts viscosity to the solution. suspension between 3.5 to 5.0. L-methionine is
Suspending agents form film around particle and decrease inter-
particle attraction. most widely used as buffering agent in parenteral
suspension.
31 32
7. Osmotic Agents: They are added to produce osmotic
pressure comparable to biological fluids when suspension is Preparation of a suspension
to be intended for ophthalmic or injectable preparation.
Most commonly used osmotic agents for ophthalmic finely divided particles
suspensions are dextrose, mannitol and sorbitol.
particles are added to dispersion medium
• The tonicity-adjusting agents used in parenteral suspension
are sodium chloride, sodium sulfate, dextrose, mannitol
wetting agent is used
and glycerol.
deflocculated suspension
8. Preservatives: The naturally occurring suspending agents
such as tragacanth, acacia, xanthan gum are susceptible to
microbial contamination. If suspension is not preserved addition of structured vehicle flocculating agents flocculating agents
properly then the increase in microbial activity may cause are added are added
stability problem such as loss in suspending activity of deflocculated suspension
suspending agents, loss of color, flavor and odor, change in in structured vehicle flocculated suspension addition of structured vehicle
elegance etc. Antimicrobial activity is potentiated at lower
pH. flocculated suspension
in structured vehicle
33 34
Evaluation of Suspensions
A) Sedimentation method: Two parameters are studied
for determination of sedimentation.
• 1. Sedimentation volume (F): sedimentation
volume of a suspension is expressed by the ratio of
the final volume of the sediment, Vu, to the original
volume, Vo of the suspension before settling.
F = Vu/Vo
• The value of F provides a qualitative knowledge
about the physical stability of the suspension.
35 36
F= 1 This is the ideal condition. No
sedimentation, no clear supernatant.
• Degree of flocculation (β): degree of flocculation
F =0.5 50% of the total volume is occupied is the ratio of the sedimentation volume of the
by sediment flocculated suspension, F, to the sedimentation
volume of the deflocculated suspension, F∞.
F>1 Sediment volume is greater than the
original volume due to formation of F Vu /Vo
β= =
network of flocs which are fluffy and F V /Vo
loose. Therefore extra vehicle is
added. • The minimum value of β is 1. The degree of
flocculation is therefore an expression of the
increased sediment volume resulting from
flocculation. Suspension having the higher β
value is the preferred formulation.
37 38
B) Re-disperseability: To quantitate this parameter D) Electro kinetic method: Measurement of Zeta-potential using Micro
to some extent, a mechanical shaking device may electrophoresis apparatus.
be used. It simulates human arm motion during • It shows the stability of a disperse system.
41 42
45 46
• For oral delivery, nanometer size particles may allow delivery of API
through the intestinal wall into the blood stream, at desired rates
and with minimal degradation in the GI tract. Insoluble particles at
these sizes may be designed to be transportable across this barrier.
Another strategy involves encapsulation of active drugs in nano-
particulate degradable polymer structures.
47