Suspension Flashcards
what is a suspension
dispersion of finely divided solid particles in a liquid medium, which may be aqueous or non-aqueous
size of coarse suspension
particle size >1 micron
size of colloidal suspension
particle size <= 1 micron
applications for suspension
- oral
- injection
- external use
oral applications of suspension
- provide means of administering insoluble drugs in liquid form
- provide means of supplying distasteful drugs in a form pleasant to taste
- provide an effective means of administering insoluble compounds for their absorptive or antacid properties in the treatment of gastric disorders
injection use of suspension
provide a means of sustaining drug release as depot therapy
external use of suspension
provide means of applying insoluble drugs to skin
desirable properties of suspension
- chemically stable
- low rate of sedimentation of particles
- particles should be readily dispersed upon gentle shaking of container
- size of particles should remain fairly constant throughout storage
- should pour readily from container
- suspensions for injection should flow readily through syringe needle
- suspensions for external use should spread easily and yet not so mobile that they run off the surface when applied
stokes law
v= (2r^2 (p1-p2)g)/9n
flocculated suspension
- aggregates in dispersed phase
- rapid sedimentation rate
- porous sediment forms on prolonged standing
- relatively large volume
- easy to redisperse
- clear supernatant liquid
- rheological property of concentrated suspension- plastic flow with thixotropy
deflocculated suspension
- individual particles in dispersed phase
- slow sedimentation rate
- compact sediment (cake) forms on prolonged standing
- relatively small volume
- difficult to redisperse
- cloudy supernatant liquid
- dilatant flow
- troublesome during production
important factors for formulation of a suspension
- dispersed phase
- liquid vehicle
- wetting agent
- flocculating agent
- thickening agent
- pH buffer
- preservative
- colorant, flavour, fragrance
dispersed phase
aka suspensoid, consisting of insoluble solid particles: lyophilic and lyophobic
lyophilic solid
solvent-loving and do not require the use of wetting agent for dispersion in the liquid vehicle; may also increase the viscosity of suspension
lyophobic solid
not solvent-loving and require the use of wetting agent for dispersion in the liquid vehicle, most drugs are hydrophobic
liquid vehicle
dispersion medium / continuous phase; may be aq or non-aq, usually is water
wetting agent
function to make the solid particles more penetrable by the dispersion medium, eg: replace air space in particle crevice - usually pre-mixed with solid particles in the preparation of suspension
moa of wetting agent
- reduce solid-liquid interfacial tension
2. imparts hydrophilicity to particle surface
examples of wetting agent for aq dispersion medium
- surfactant: HLB 7-9 (eg. spans), used at concentrations below CMC
- hydrophilic polymers (eg. acacia, tragacanth xanthan gum, polyvinylpyrrolidone)
- polyhydric alcohols: miscible with water (eg. glycerin, propylene glycol, polyethylene glycols)
flocculating agents
- electrolytes
- surface-active agents
- hydrophilic polymers
electrolytes
affect the zeta potential which governs interparticulate repulsion/attraction, interparticulate attraction occurs when zeta potential is reduced below critical value
low concentration of electrolyte
- 01-1%:
- generally sufficient to reduce the zeta potential to just below the critical value for interparticulate attraction to occur
- van da 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
high concentration of electrolyte
- reverse the sign of 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
valence of electrolyte
effectiveness of electrolyte in aggregating particles increases with valence of ions
- divalent ions are 10 times while trivalent ions are 100 times as effective as monovalent ion
- monovalent ions are sufficient to induce flocculation of weakly charged particles
surface-active agents
- ionic agents- behaving like electrolyte
- non-ionic agents- used at concentration above cmc, micelles adsorbed at surface of the particles, where they serve as bridges between particles; flocculation brought about by bridging mechanism between particles
thickening agent
function to assist suspension of solid particles, achieved through thickening of dispersion medium
example of thickening agent
gums, gelatin, bentonite, carboxymethyl cellulose, polyvinylpyrrolidone
small scle dispersion techique
- mix solid drug with wetting agent in mortar
- add a small portion of liquid vehicle containing the additives to produce a pourable mixture
- transfer the mixture to measuring cylinder and make up to the required volume with remainder of the liquid vehicle
large scale dispersion technique
- add wetting agent to solid (drug) in mixer
- add liquid vehicle containing additives
- transfer the mixture to high shear equipment to produce a good dispersion (excessive shearing should be avoided)
precipitation technique
- 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 whos solubility affected by ph
stability of suspension
index of stability (F) = Volume of sediment at time t / initial volume of total suspension = Ht/Ho
more stable- less change in F over time
redispersibility of suspension
- mechanical device is used to shake the suspension which has been put aside for dispersed phase to settle down
- the number of shakes required to disperse the sediment is determined
- ease of dispersibility is inversely proportional to the number of shakes
hydrophilic polymer examples
Acacia, tragacanth, alginates
low concentration hydrophilic polymers
<0.05%
- generally sufficient to bring about flocculation
- adsorbed at surface of particles, where they serve as bridges between particles
high concentration hydrophilic polymers
1 protective colloid effect 0.05-0.1%: polymer forms a protective coat around each particle, separating them from one another
2. viscosity-enhancing effect >0.1%: polymer increases the viscosity of the medium and improve stability but reduces flowability of the suspension
