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Flashcards in Suspensions Deck (27)
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1

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

2

Two types of suspensions

Coarse suspension > 1um
Colloidal suspension <= 1um

Liquid and be aq or non aq

3

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

4

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.

5

Deflocculated
And
Flocculated suspension

Particles types

Deflocculated
= dispersed particle

Flocculated
=floccules

6

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

7

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.

8

Formulation of suspension requires

Dispersed phase
Liquid vehicle

Wetting agent
Flocculating agent
Thickening agent

pH buffer
Preservative
Colorant, flavor and fragrance

9

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.

10

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.

11

Concentration of wetting agent required

Below CMC of surfactant

12

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.

13

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

14

Wetting agent that should not be used

Diethylene glycol
- kills children
- antifreeze

15

Types of flocculating agents

Electrolytes
Surface active agent
Hydrophilic polymers

16

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.

17

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)

18

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.

19

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.

20

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.

21

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% )

22

Shear equipments

Colloid mill
Turbine mixer

Propeller mixer is inadequate

23

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.

24

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.

25

How to evaluate suspension

Stability of suspension
Redispersibility of suspension

26

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

27

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.