Pharmaceutical Suspensions

(The formulation of Suspensions)

PART 1: PHYSICOCHEMICAL PRINCIPLES

DRABE NICKSON.,(M.P.S)
 Lecture objectives
• To discuss the advantages and disadvantages of suspensions

• To discuss the theory of suspensions as a disperse system

• To discuss the physical stability of suspensions

• To discuss the formulation techniques employed to stabilize

pharmaceutical suspensions
 Introduction
• A suspension is a two-phase disperse system in which a solid material (the
disperse phase) is distributed in a liquid (the dispersion medium/continuous phase)

• A suspension enables drugs with poor solubilities to be formulated as liquid

dosage forms

• The diameter of the disperse phase may range from 0.5 to 100 m

• Systems in which the particle size diameter falls below the above range are termed
colloidal
Some examples of products that are
suspensions !
 Features of an acceptable suspension
• Low particle sedimentation rate

• Disperse phase must be easily redispersed with gentle shaking

• Flow properties should enable ease of removal from the container

• Aesthetically pleasing
 Advantages of suspensions as a dosage form

• Enable drugs with poor solubilities to be formulated as liquid dosage

forms

• Suspensions may be formulated to mask the taste of therapeutic agents

• May be employed to achieve controlled drug delivery e.g. IM injections

Disadvantages of suspensions as a dosage form

• Fundamentally unstable requiring formulation skill to retain physical

stability of the formulation over the shelf-life

• The formulation of aesthetic suspension formulations is difficult

• May be bulky and therefore difficult for a patient to carry around

 The Suspension theory
(Basis of instability)
• Water-insoluble drugs in fine dispersion form lyophobic disperse systems

• These are thermodynamically unstable because of their high surface

energy thus have a tendency to aggregate or flocculate to reduce total
surface area

.,Where
 Basis of instability cont’d…
• Suspended particles also sediment over time under the action of
gravity
• Sedimentation occurs in accordance to Stokes’ Law as shown below
• where; ν-sedimentation velocity
a-particle radius
-density of the particle
-density of the dispersion medium
-acceleration due to gravity
-coefficient of viscosity of the medium
 Solid particle–liquid vehicle interactions
(The net surface charge of particles)
Most particles acquire a surface electric charge in an aqueous medium. The principal
charging mechanisms are the following;-

Ion dissolution; unequal(differential) dissolution of oppositely charged ions from the

surface of an ionic substance.

Ionization; charge acquired by ionization of ionizable functional groups e.g.-COOH or

–NH2

Selective adsorption; unequal(differential) adsorption of oppositely charged ions

imparting a net surface charge
 Solid particle–liquid vehicle interactions…
(The ‘electrical double layer’ theory)
First (Stern) layer;
• Ions, e.g. anions, are adsorbed on to the surface of the particle generating a potential
termed the Nearnst potential ψ0.

• Such ions are termed potential-determining ions.

• Cations (counterions) are then electrostatically attracted to the negative surface of the
particle.

• The boundary of this layer is the stern plane at a distance equal to the radius of a hydrated
counterion. The potential at this point is the Stern potential ψ
The ‘electrical double layer’ theory…cont’d
Second (Gouy-Chapman) layer
• Predominantly contains hydrated counterions loosely attracted to the particle

• The boundary of this second layer possesses a potential termed the zeta
potential ξ

• If the particle is rotated, this second layer forms the shear plane, i.e. the
effective surface.

• Usually, ψ0ψ
• Eventually, at a certain distance electrical neutrality is restored
The ‘electrical double layer’ theory…cont’d
 Find out !

Apart from electrolyte concentration in the dispersion

medium, are there other factors that affect the double
layer thickness?
 Interactions between particles
(The DLVO theory)

• Quantitatively described by Derjaguin, Landau, Verwey and Overbeek thus

DLVO
• Assumes that dispersed particles will experience repulsive forces and
attractive forces

• Overall energy of interaction between the particles (VT) can be described as

an addition of the energies of attraction (VA) and repulsion (VR)
VT=VA+VR
 The DLVO theory cont’d…
Energy of attraction;
• is due to van der Waals forces
• operates at greater distances than the repulsive forces

Energy of repulsion;
• is due to the overlap/interaction between the electrical double layers
of each particle
• operates over a distance of approximately the thickness of the double
layer.
The DLVO plot
 The DLVO plot cont’d…
The primary minimum
• This is a region of high attraction between particles
• Particles will irreversibly coagulate and the formulation will be physically
unstable

The primary maximum

• This region prevents the particles from interacting at the primary minimum
• The magnitude is controlled by the zeta potential at the shear plane
 The DVLO plot cont’d…
The secondary minimum
• Attractive forces predominate but the magnitude of the attraction is less than that
at the primary minimum

• Interaction at this distance allows for flocculation

• Such loose aggregates of particles are called floccules and can be redispersed on
shaking

• The act of engineering particles to reside in the secondary minimum is referred to

as controlled flocculation
 QUESTION FOR YOU!

1. What is the main pharmaceutical advantage of a

flocculated state in a suspension?
2. By what technique can a formulation scientist achieve
controlled flocculation? Explain how the technique works.
 DONE HERE !
CONTINUE PART 2;
STABILIZATION OF SUSPENSIONS & ROLE OF EXCIPIENTS
PER MEDICATUM SERVIUM