Suspensions Flashcards
What is suspension
A suspension is a dispersion of finely divided solid particle in a liquid medium.
The solid particle does not dissolve appreciably in the liquid medium
Two types of suspensions
Coarse suspension > 1um
Colloidal suspension <= 1um
Liquid and be aq or non aq
Application of suspension
1) oral
- masked unpleasant taste
- for their absorptive properties
2) IV
- depot therapy ( to provide slow release / sustained release)
3) external use
- provides a mean to apply insoluble drugs to skin
Desired properties of suspensions
Chemically stable.
Low rate of sedimentation of particles.
Particles should be readily redispersed upon gentle shaking of container.
Size of particle should remain fairly constant throughout storage.
Should pour readily from container.
Suspensions for injection should flow readily through a
syringe needle.
Suspensions for external use should spread easily and yet not so mobile that they run off the surface when applied.
Deflocculated
And
Flocculated suspension
Particles types
Deflocculated
= dispersed particle
Flocculated
=floccules
Properties of flocculated suspension
Nature of dispersed phase
Sedimentation rate
Nature of final sediment
Nature of supernatant liquid
Theological properties of concentrated suspension
Aggregates
Rapid
A porous sediment forms on prolong standing.
Relatively large volume
Easy to disperse
Clear
Plastic flow with thixotropy
Properties of deflocculated suspension
Nature of dispersed phase
Sedimentation rate
Nature of final sediment
Nature of supernatant liquid
Theological properties of concentrated suspension
Individual particles
Slow
A compact sediment (cake) forms in prolong standing
Relative small volume
Difficult to redisperse
Cloudy
Dilantant flow.
Troublesome during production.
Formulation of suspension requires
Dispersed phase
Liquid vehicle
Wetting agent
Flocculating agent
Thickening agent
pH buffer
Preservative
Colorant, flavor and fragrance
Types and property of the dispersed phase (suspensoid)
(i) Lyophilic solids
o Solvent-loving and do not require the use of wetting agent for dispersion in the liquid vehicle.
o May also increase the viscosity of suspension.
(ii) Lyophobic solids
o Not solvent-loving and require the use of wetting agent for dispersion in the liquid vehicle.
o Most drugs are hydrophobic.
W/O Wetting agent particles will float on top.
(Most hydrophobic drug when dispersed as solid particles in an (aq) environment will acquire a charged. Due to ionization of water.
Why need wetting agent
In order to reduce Surface tension and obtain a more energetically favorable situation, solid particle tend to clump together. So that the total particulate SA in contact with water is reduced. Hence the total surface tension is reduced.
As a result, product is inhomogenous, inelegant, and reproducible dosing is not possible.
Thus wetting agent is needed.
Concentration of wetting agent required
Below CMC of surfactant
Function of wetting agent?
To make solid particle mode penetrable by the dispersion medium by
- lowering solid-liquid interfacial tensions
- impart hydrophilicity to particle surface.
Example of wetting agent
Usually premixed with the solid particles
- surfactant (HLB 7-9) e.g. Spans
Use at concentration below CMC
-hydrophilic polymers
E.g. Acacia, tragacanth, xanthan gum, Polyvinylpyrrolidone.
-polyhydric alcohols
Miscible with water
E.g. Glycerin, propylene glycol, PEG
Wetting agent that should not be used
Diethylene glycol
- kills children
- antifreeze
Types of flocculating agents
Electrolytes
Surface active agent
Hydrophilic polymers
How Electrolyte as flocculating agent affects flocculation
And the properties that affect
Affects the zeta potential which governs interparticulate repulsion/attraction
Interparticulate attraction occurs when zeta potential is reduced below a critical value
The concentration and valence of the electrolytes affects the flocculation.
Concentration effect of electrolyte as flocculating agent
(i)Concentration of electrolyte
Low concentration (0.01 – 1 %):
Generally sufficient to reduce the zeta potential to just below the critical value for interparticulate attraction to occur.
van der Waals attractive forces cause the solid particles to aggregate to form flocs.
On prolonged standing, the flocs will settle to form a porous sediment which is easy to redisperse.
(Flocculation)
High concentration:
Reverses the sign of the zeta potential and to a magnitude that will cause interparticulate repulsion.
On prolonged standing, the particles will settle and form a compact sediment which is difficult to
redisperse.
(Deflocculation)
Valence of electrolytes on flocculation
(ii) Valence of electrolyte
According to the Schulze-Hardy rule, the effectiveness of electrolyte in aggregating the particles increases with the valence of the ions.
Divalent ions are 10 times while trivalent ions are 1000 times as effective as monovalent ions.
Monovalent ions are sufficient to induce flocculation of weakly charged particles.
How surface active agents
Affect flocculation
2) Surface active agents
(i) Ionic agents (affect zeta potential)
They behave like electrolytes.
(ii) Non-ionic agents (do not affect zeta potential)
Used at concentration above cmc.
The micelles are adsorbed at the surface of the particles, where they serve as bridges between particles.
Flocculation is brought about by a bridging mechanism between the particles.
Factors affecting hydrophilic polymers as flocculating agent
(3) Hydrophilic polymers
Examples: acacia, tragacanth, alginates
Low concentration (<0.05%)
o Generally sufficient to bring about flocculation.
o They are adsorbed at the surface of particles, where
they serve as bridges between particles.
High concentration
o This will result in other effects:
Protective colloid effect (0.05-0.1%)
Polymer forms a protective coat around each particle, separating them from one another.
Viscosity-enhancing effect (>0.1%)
Polymer increases the viscosity of the medium and improves stability but reduces flowability of the suspension.
Function of thickening agent
Example
And
Factors affecting thickening agent
Thickening agent
Its function is to assist in the suspension of the solid particles.
This is achieved through thickening of the dispersion medium.
E.g. gums, gelatin, bentonite, carboxymethyl cellulose, polyvinylpyrrolidone
Depending on the concentration used, the hydrophilic polymer may exert other effects
Flocculating effect (<0.05%)
Protective colloid effect ( 0.05-0.1% ) Viscosity-enhancing effect( >0.1% )
Shear equipments
Colloid mill
Turbine mixer
Propeller mixer is inadequate
Steps in preparing suspension using the dispersion technique
Mix the drug (solid) with wetting agent
Add liquid vehicle containing additives.
Transfer to cylinder / shear equipment to produce a good dispersion.
Precipitation technique
Preparation of suspensions
(2) Precipitation technique
(Uncommon)
Organic solvent precipitation
Water-insoluble drug is dissolved in water-miscible organic solvent and then added to distilled water under standard conditions.
pH-induced precipitation
Only applicable to drugs whose solubility is affected by pH.
How to evaluate suspension
Stability of suspension
Redispersibility of suspension
Stability of suspension
F=Vt/Vo
F= index of stability Vt= volume of sediment at time t Vo = initial volume of total suspension
Vt/Vo = ht/ho
Time 0= F=1
Redispersibility of suspension
2) Redispersibility of suspension
A mechanical device is used to shake the suspension which has been put aside for the dispersed phase to settle down.
The number of shakes required to disperse the sediment is determined.
The ease of redispersibility is inversely proportional to the number of shakes.
