SUSPENSIONS/

PHARAMCEUTICAL SUSPESIONS

Prof. Dr. Muhammad Jamshaid

Dean FOP-UCP
Definition
Combination of insoluble substances or drugs (solids)
and liquid as continuous or dispersion medium.

Solid insoluble phase is dispersed or distributed as a

dispersed phase into liquid as a dispersion medium
Nature
Coarse dispersion in which size of the dispersed phase
is > 500nm.

Note: Submicron polymer dispersions are also

available
Purpose

Used orally

As injectable form I/M or S.C.

Drug reservoir as Transdermal patches

Topical formulations

Aerosols (suspensions of drugs in propellants)

 Problems
Instability leading to uneven distribution of dispersed
phase [drug(s) in case of Pharmaceutical suspension(s)]

This may be as:-

Sedimentation
Caking (Difficulty in re-dispersion)
Flocculation (Irreversible)
Particle growth (Through dissolution and re-
crystallization)
Adhesion of particles to container walls (Important
for low dose drugs)
Overcoming the problem of caking
 General desire to avoid aggregation of particles in suspension and in
Lyophilized preparations.
 Redispersibility of suspension.
 Flocculated system development to overcome. i.e. particles held
together in a loose open structure.
Two systems i) Flocculated
ii) Deflocculated
 In flocculation, rapidly clearing supernatant so not elegant and
unsightly suspension.
 In deflocculation, free particles tend to settle down and pressure on
them will lead to cake formation.
Therefore……partially deflocculated suspensions are ideal
preparations.
Viscosity is affected by flocculation.
Special Suspensions in the field of Drug Targetting/
Site Specific Drug Delivery System

(Liposomes, niosomes, microspheres, microcapsules

and nanoparticles…… prepared from polymers and

proteins) (Drug carriers)

Stability of Suspension
Vs h
R = ----- ----- ~
~
Vt h0
R = Ratio
Vs = Sedimentation volume
Vt = Total volume
h = Height of sedimented layer
h0 = Initial height A
h0
--------
-------- Clarified zone Hindered
………….. settling
.................. Discrete particle settling
................

Compression
/////////////////
///////////////// Hindered settling B
h0
“””””””””” Transition zone C
”””””””””” Transition
””””””””
********* Compression
********* h D
******
++++++++++
++++++++
Sedimented layer
Bottom
h
 Factors
Factors governing the suspension stability are almost similar
to emulsions (both….. Disperse systems)
However …… differences are there:
Parameter Emulsion Suspension
Coalescence occur not occur
Creaming +ve -ve
Flocculation both reversible reversible
and irreversible
Also, adsorption behavior is different in emulsion than in suspensions
 Caking -ve +ve in
deflocculated systems
Role of viscosity in suspension stability/
suspension settling
Movement of particles:
In viscous medium fine particles move slowly than flocculated
particles but form more firm cake due to:
- close packing
- pressure onto particles
- filling the voids.
 Stoke’s law:
Larger particles settle more rapidly than finer ones, under the
influence of gravity.
V= average velocity of sedimentation
d= diameter of particles
ps= density of solid phase
pp= density of liquid phase
n= viscosity of the medium
g= acceleration due to gravity
Limitations
Equation works only for very dilute suspension having
spherical particles, i.e.; settling occurs without
interfering of particles known as “Free settling”
In practice suspensions are:-
- usually concentrated
- particles are not generally spherical
So interference of particles during settling known as
“Hindered settling”
Also, no turbulence should be there in the system.
Limitations--- settling/sedimentation
Faster rate of settling/ sedimentation if:-

a) bigger particles

b) greater difference between “ps” & “pp”

Slow rate of settling if:-

a) smaller particles

b) small difference between “ps” & “pp” along

with higher viscosity of the suspension.
Sedimentation/ settling behavior of Flocculated
and Deflocculated suspensions

A) Sedimentation rate: The rate is high in flocculated

system than deflocculated system due to the

formation of bigger clumps.

B) Nature of sediment: In flocculated system,

aggregation loose open structure and entrapping

liquids.

In deflocculated system settling gives rise to cake

formation …………… difficult to redisperse.
 Flocculated system Deflocculated system
………
Clear supernatant layer ………
………
………
/////////// Clear-cut boundary ……… No change occur
With in
/////////// ………
minutes /////////// between two layers ……… within minutes
/////////// ………
/////////// ………
/////////// Sedimenting layer ………
/////////// …….
/////
……… Cloudy supernatant
Clear supernatant layer ………
……… layer
………
With in ………
hours Flocculated/ sedimented ----------
---------- Density/ con. of
----------
----------
/////////// layer of large vol. having ----------
---------- particles increase in
/////////// ----------
----------
/////////// liquid entrapped ----------
---------- this portion
/////////// ----------
--------
//

Clear supernatant layer Clear supernatant

With in layer
weeks
Sedimented layer
----------
---------- Sedimented layer
/////////// (no change in sedimented ----------
----------
/////////// ----------
---------- Cake formation
/////////// layer) ----------
--------
/
Prediction of stability of suspension
through…….Zeta potential
Flocculating agents prevent caking
Deflocculating agents promote caking

Measurement of Zeta potential of particles in

suspensions…….. Monitor the addition of flocculating and
deflocculating agents.

“Creation of charge on particles”

i) By adsorption of ions.
ii) By ionization (pH is important factor)
iii) Repulsive forces due to electrical double layers on
adjacent particles
Measurement of Electrophoretic Mobility of
Particles
Magnitude of the charge can be determined by measuring
Electrophoretic Mobility of particles in an applied electric
field by:
i) Electrophoresis
ii) Zeta Sizer (same principle)
Zeta Potential is not surface charge but related to it.
Any factor changing viscosity will affect surface charge
so Zeta Potential can be used as a guide to the magnitude of
Electric Repulsive Forces between particles.
Change in “ ζ “ by flocculating agent/ surfactant can then be
used for prediction of stability
“Controlled Flocculation” or Partial
Deflocculation or Partial Floccualtion
Example: Bismuth subnitrate suspension
Flocculating agent: Dibasic potassium phosphate
Zeta Potential: Positive on the suspension.
Non-caking
Caking zone zone Caking zone

++++ + ----
-O-

Controlled floccualtion of Bismuth subnitrate

+ +O+ +O+ ----
++++ Note: Bismuth compound treats G.I. problems
Flocuculating

especially Peptic ulcer.

Colloidal Bismuth sub citrate (CBS) has direct

Zeta potential

action as antimicrobial agent against ”Helicobecter

zone

Sediment height
Pylori”

ho
___________
CBS medium Bismuth oxychlor + bismuth citrate
h
acidic
------------------------------------- -------------------------------------
------------------------------------- -------------------------------------
------------------------------------- -------------------------------------
------------------------------------- -------------------------------------
------------------------------------- -------------------------------------
---------------------------- ----------------------------

Inhibition of action of pepsin

possibly due to adsorption of pepsin on bismuth oxychlor
Non Caked

suspension
-
Caked

Caked

Conc. of KH2PO4
Controlled Flocculation
Example: Sulphamerazine suspension
Deflocculating agent: Dioctyl sodium sulphosuccinate
Controlling flocculating agent: Aluminium chloride
Deflocculation
Controlled
flocculation { reduced
+AlCl3

Hains and Martin’s Interpretation

+ dioctyl sodium Deflocculation
sulphosuccinate

Controlled (clumps)
Deflocculation

+AlCl3
Controlled
flocculation
{ Deflocculation
reduced
 Controlled Flocculation--- contd.

+ AlCl3
Bonds between
flocculated particles

Controlled
flocculation

Dioctyl sod. sulphosuccinate Al+ ions reacts Controlled

adsorption with dioctlyl … flocculation

Viscosity controlled by thickners e.g. gum acacia, CMC sod.

 Pharmaceutical Applications of Suspensions

Suspensions are prepared:-

- in final form and stored for long time

(finished products)

- at the time of use e.g. Ampicillin suspension

(extempore preparation)

“In final form, contact of particles and dispersion medium

increases causing unwanted effects. So, reconstituted powders are
supplied for mixing with H2O.”
 Pharmaceutical Applications of Suspensions –contd.
Oral Administration of Suspension:-
 where solid dosage forms (tablets and capsules) are different to
swallow.
 For adsorptive purpose e.g. Kaolin, MgCO3, Mag. trisilicate etc.
are used as antacid locally.
 Insoluble derivatives are often used to avoid unpleasant taste of the
drug e.g. use of chloramphenicol palmitate instead of its base.
 Suspension for injection:-
 For depot therapy.
 Suspension for external use:-
 Lotion (pourable ext. prep.) e.g. calamine lotion,
 Paste (semisolid characteristics) e.g. MagSO4 paste, Zinc & Salicylic acid paste.
 Extemporaneous Suspensions

Extemporaneous preparation of suspensions of drugs generally/

normally available commercially in other dosage forms.

Extemporaneous preparations of such drugs in suspension form

are widely practiced in hospitals particularly for paediatrics use.

Drugs like Acetazolamide (Diuretic), Amiodarone (antiarrhythmic

and antianginal agent), mercaptopurine (anticancer drug
particularly treatment for childhood acute leukemia), Sotalol
(antiarrhythmic), and Warfarin (oral anticoagulant) are common
examples.
 Extemporaneous Suspensions

In such formulations alternatives to traditional suspending agents

(e.g. gum tragacanth) are examined like…… Sod. carboxy methyl
cellulose (sod. CMC), microcrystalline cellulose (Avicel),
Aluminium magnesium silicate (Veegum), Sod. alginate
(Manucol) and Sod. starch (primojel).

Based on sedimentation volume and redispersibility,

pregelatinized starches, primojel and veegum, are promising
alternatives suspending agents.
 Characteristics of suspending agents

The Ideal suspending agent should:-

 be readily dissolved or dispersed in water.

 ensure the formation of loosely paced system.
 not influence the dissolution rate/ absorption rate of the drug.
 be inert, non-toxic and free from incompatibilities.
 be readily and uniformly incorporated in formulation.