SUSPENSI

BLOK 12
APT. DYANI PRIMASARI S, M.SC.
BLOK 12

SUSPENSI (PART 1)
Definisi
• Suatu sediaan cair yang berisi suatu partikel solid yang tidak larut dan
terdispersi dalam suatu fase cair.

• A Pharmaceutical suspension is a coarse dispersion inwhich internal

phase is dispersed uniformly throughout the external phase.

• Suspensions are a class of dispersed system in which a finely divided

solid is dispersed uniformly in a liquid dispersion medium (Nash 1988).
• The internal phase consisting of insoluble solid
particles having a specific range of size which is
maintained uniformly through out the
suspending vehicle with aid of single or
combination of suspending agent.

• The external phase (suspending medium) is

generally aqueous in some instance, may be an
organic or oily liquid for non oral use.

• Suspensions can be classified as coarse or

colloidal dispersion, depending on the size of
particles.
• A wide variety of pharmaceutical preparations have been used as
suspensions, for example, White Lotion, Magma of Bismuth, and
Compound Mixture of Opium and Glycyrrhiza (Brown Mixture).
• In addition, several official ointments are suspensions of solids in a
semisolid base.
• A large number of suspensions are categorized as mixtures in the
United States Pharmacopeia and the National Formulary.
Classification
1. Based On General Classes
– Oral suspension
– Externally applied suspension
– Parenteral suspension
2. Based On Proportion Of Solid Particles
– Dilute suspension (2 to10%w/v solid)
– Concentrated suspension (50%w/v solid)
3. Based On Electrokinetic Nature Of Solid Particles
– Flocculated suspension
– Deflocculated suspension
4. Based On Size Of Solid Particles
– Colloidal suspension (< 1 micron)
– Coarse suspension (>1 micron)
– Nano suspension (10 nm)
Advantages And Disadvantages
Advantages

• Suspension can improve chemical stability of certain drug. E.g.Procaine penicillin G

• Drug in suspension exhibits higher rate of bioavailability than other dosage forms.
bioavailability is in following order,

Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

• Duration and onset of action can be controlled. E.g.Protamine Zinc-Insulin suspension

• Suspension can mask the unpleasant/ bitter taste of drug. E.g. Chloramphenicol

Disadvantages

• Physical stability,sedimentation and compaction can causes problems.

• It is bulky sufficient care must be taken during handling and transport.

• It is difficult to formulate

• Uniform and accurate dose can not be achieved unless suspension are packed in unit dosage
form
Features Desired In Pharmaceutical Suspensions
• The suspended particles should not settle rapidly and
sediment produced, must be easily re-suspended by the
use of moderate amount of shaking.
• It should be easy to pour yet not watery and no
grittiness.
• It should have pleasing odour, colour and palatability.
• Good syringeability.
• It should be physically, chemically and
microbiologically stable.
• Parenteral/Ophthalmic suspension should be
sterilizable.
The following can be the reasons for the formulation of a
pharmaceutical suspension:

– The drug is insoluble in the delivery vehicle.

– To mask the bitter taste of the drug.
– To increase drug stability.
– To achieve controlled/sustained drug release.
Applications
• Suspension is usually applicable for drug
which is insoluble or poorly soluble.
E.g.Prednisolone suspension

• To prevent degradation of drug or to improve

stability of drug. E.g. Oxytetracycline
suspension

• To mask the taste of bitter of unpleasant drug.

E.g. Chloramphenicol palmitate suspension
• Suspension of drug can be formulated for
topical application e.g. Calamine lotion

• Suspension can be formulated for parentral

application in order to control rate of drug
absorption.

• Vaccines as a immunizing agent are often

formulated as suspension.E.g. Cholera vaccine

• X-ray contrast agent are also formulated as

suspension. E.g. Barium sulphate for
examination of alimentary tract
Berbagai bentuk sediaan suspensi untuk
penghantaran obat

• Suspensi konvensional
• Sustained Release Suspensions
• Emulsions
• Colloidal Dispersions
– Micelles
– Microemulsions
– Nanosuspensions
– Liposomes
– Nanoparticles
– Microspheres
• Velocity of sedimentation expressed by Stoke’s equation

Where, vsed. = sedimentation velocity in cm / sec

d = Diameterof particle
r = radius of particle
ρ s= density of disperse phase
ρ o= density of disperse media
g = acceleration due to gravity
η o = viscosity of disperse medium in poise
Pertimbangan-pertimbangan yang penting
dalam memformulasi suspensi
1. Nature of suspended material
– Particles that have low interfacial tension are easily wetted by water and there are
can be suspended easily.
– Particles of materials with high interfacial tension, however, are not easily wetted.
2. Size of suspended particles
– The particle diameter in a suspension is usually
greater than 0.5 m.
– Reduction of particle size leads to a decrease in the
rate of sedimentation
– Particle size also affects rate and extent of
absorption, dissolution, and biodistribution of the
drug
– reducing particle size beyond a certain limit may
lead to formation of a compact cake upon
sedimentation.
– suspensions may have smaller particles than 0.5 m
and may show some characteristics typical to
colloidal dispersions, such as Brownian movement
3. Viscosity of the dispersion medium
– Greater viscosity of dispersion medium offers the
advantage of slower sedimentation
– it may compromise other desirable properties such as
syringability for parenteral suspensions, spreadability
for topical suspensions, ease of administration for oral
suspensions
An ideal suspension formulation
• Insoluble particles should be uniformly dispersed.
• Suspension should redisperse uniformly in the
continuous phase, upon moderate shaking
• Correct amount of medication with minimal dose
variation.
• The rate of settling can be decreased by using viscosity
improving agents,
• Ease of redispersibility can be controlled by using
flocculating agents.
• The suspended particles should be small, uniformly sized
to give a smooth elegant product free from grittiness.
 Interfacial Properties
• Surface Free Energy

Where

G = increase in surface free energy,

 A = increase in surface area,

 = interfacial tension between the solid articles and the dispersion medium.

The smaller the DG is, the more thermodynamically

stable is the suspension
• Therefore, a system with very fine particles is
thermodynamically unstable because of high total surface
area.

• Thus, the system tends to agglomerate in order to reduce

the surface area and thereby the excess free energy.

• When a wetting agent is added to the suspension

formulation, it is adsorbed at the interface. This will
result in a reduction of the interfacial tension, making the
system more stable.
• Surface Potential
– Surface potential exists when dispersed solid particles
in a suspension possess charge in relation to their
surrounding liquid medium.

– Solid particles may become charged through different

ways

– the surface active agents, which are already adsorbed at

the solid–liquid interface, may ionize to give the
particles positive or negative charge.

– Sodium dodecyl sulfate (SDS), for example, is anionic

in aqueous medium.

– Solid particles can also be charged by ionization of

functional group of the particles.
Electric Double Layer
• When dispersed particles are in contact with an aqueous
solution of an electrolyte, the particles may selectively
adsorb one charge species.

• If the adsorbed species is an anion, the particles will be

overall negatively charged.

• The ions that give the particle its charge, anions in this
case, are called potential-determining ions or co-ions.

• Remaining ionic species in the solution are the rest of the

anions and the total number of cations added.

• This means, there will be excess cations than anions in

the dispersion medium. These cations having a charge
opposite to that of the potential-determining ions are
known as counter-ions or gegenions.
Nernst and Zeta Potentials
• The electric double layer is formed in order to neutralize
the charged particles in a suspension.

• The difference in electric potential between the actual or

true surface of the particle and the electroneutral region is
referred to as the surface or electrothermodynamic or
Nernst potential (E)

• Hence, Nernst potential is controlled by the electrical

potential at the surface of the particle due to the potential
determining ions.

• The potential difference between the shear plane and the

electroneutral region is known as the electrokinetic or
zeta (z) potential
Variation in concentration of cations and anions with distance
from a negatively charged suspended particle
The relationship between Nernst and zeta potentials
• While Nernst potential has little influence in the
formulation of stable suspension, zeta potential
has significant effect on it

• Zeta potential governs the degree of repulsion

between adjacent, similarly charged solid
dispersed particles.

• If the zeta potential is reduced below a certain

value, which depends on the specific system
under investigation, the attractive forces between
particles due to van der Waals’ force, overcome
the forces of repulsion and the particles come
together to form floccules.

• This phenomenon is known as flocculation.

Wetting
• Low adhesion of hydrophobic powders materials
occurs due to high interfacial tension between
the powders and the dispersion medium.

• Because of this tension, the contact angle between

the solid and liquid phases remains very high.

• By using surface active agents, the interfacial

tension can be lowered to decrease the contact
angle, resulting in good wetting.

• Wetting of solids can be determined by using

Young’s equation:
• Some insoluble solids are not easily wetted by water and thus need
wetting agents to be able to disperse readily throughout the medium.

• Some wetting agents include surfactants, hydrophilic colloids, and

solvents.

• Surface active agents or surfactants possessing HLB value between 7

and 9 are suitable as wetting agents.
Bersambung……