suspensions Flashcards
suspension definition
finely divided solid particles dispersed in liquid medium
coarse vs colloidal suspension particle sizes
coarse > 1 micron
colloidal is 1 micron or less
what kind of medium normally used for suspensions
can be aq or non aq but pharm suspensions normally are aq
suspensions oral use
- administer insoluble drugs in liquid form
- supply distasteful drugs in a form w pleasant taste
- administer insoluble compounds for their absorptive or antacid properties in the treatment of gastric disorders
eg activated charcoal which absrobs toxins , mg hydroxide aloh , calcium carb or sodium bicarb etc
suspensions for injection
- sustaining drug release as depot therapy - meaning release in slow and sustained manner
suspensions for external use
means for applying insoluble drugs to the skin
desirable properties of suspensions (7)
stabl
low sedimentation rate
easily redispersed upon shaking
size of particle shld remain fairly constant throughout storage
pour readily
suspensions for injection shld flow readily thru needle
suspensions for external shld spread easily but not run off surface of site
which trait preferred for suspensions and why
thixotropy
recall stokes law
v = 2r^2(p1-p2) g / 9n
velocity radius of particle density of particle- density of dispersion medium gravitational constant (6.67 x 10^-11) viscosity of dispersion medium
recall why stokes law not directly applicable
but what can be done
- used for isolated sphere in infinitely large mass of liquid but factors can help to modify sedimentation rate
eg - inc size of particle
inc viscosity of the medium
dec the difference in density - altho hard to modify
dispersed particles and floccules form what kidn of suspension
and differentiate them according to - sedimentation rate nature of final sediment nature of supernatant liquid rheological property of conc suspension
floccules form flocculated suspension ( like clotted )
deflocculated form deflocculated suspension ( cloudy )
flocculated - rapid sedimentation rate - forms porous seidment on standing large volume bc of big interparticular space and is easy to redisperse - clear supernatant - plastic flow with thixotropy
deflocculated
- slow sedimentation rate
- forms a cake ( compact sediment ) on standing
small volume and difficult to redisperse
- cloudy supernatant
- dilatant flow !! troublesome
how to determine degree of flocculation
- allow suspension to stand til vol of sediment becomes constant V t
- centrifuge and determine volume of sediment ( Vc)
( this breaks down the flocs due to centrigual force
forming a compact, space reduced to min ) - greater the ratio of Vt to Vc = greater flocculation
whats needed in the formulation of suspensions 5 + 3
dispersed phase liquid vehicle wetting agent flocculating agent thickening agent other additives : ph buffer, preservatives, colourants flavour or fragrance
dispersed phase 2 types and what they consist of
- aka suspensoid
- consist of insoluble solid particles
lyophilic - solvent loving and dont need wetting agent for dispersion
- may inc viscosity
pyophobic - not solvent loving and needs wetting agent for dispersion
- most drugs are hydrophobic
note that solvent loving dosent mean soluble
liquid vehcile aka
what type and
commonly used
- aka dispersion medium or cont phase
may be aq or non aq
water commonly used
wetting agent func and 2 MOA
make solid particle more penetrable by the dispersion medium
moa 1: reduce solid liquid interfacial tension
moa 2- imparts hydrophilicity to the solid particle surface
imagine there are air crevices around the particle the wetting agent fills that up
when are wetting agents added
mixed in with the solid particles in the preperation
3 examples of wetting agents
- surfactants of hlb 7-9 aka spans
used @ conc below the cmc - hydrophilic polymers like acacia, tragacanth, polyvinylpyrolidone and xanthan gum
- polyhydric alcohols
- misicble w water
for eg glycerin , propylene glycol, polyethylene glycols
what is not allowed in oral suspensions due to toxic effects
diethylene glycol
3 types of flocculating agents
electrolytes
surface active agents
hydrophillic polymers
moa for electrolytes
1st class of flocculating agents
- affect Zeta potential which governs the interparticulate attraction or repulsion
- if zeta potential is reduced below critical value
= attraction
if low conc of electrolytes 0.01-1%
- sufficient to reduce ZP below critical conc
= int part attraction
= VD forces cause solid particles to aggregate and floc
= upon settling flocculates aggregates form which are easily redispersed
if high conc used
- reverses the sign of ZP til int pat repulsions occurs
- upon standing forms compact sediment which is difficult to redisperse
valency also v impt according to schulze -hardy rule
monovalent
divalent x 10
trivalent x 1000 more effective as aggregating particles
monovalent sufficient to induce flocculation if particles are weakly charged
moa of surface active agents
2nd class of flocculating agents 2 types if ionic then they behave as electrolytes
if non ionic
- must be used at conc above cmc
- micelles adsorb onto surface of particles
= serve as bridges
= bridging mechanism allowed flocculation to occur
diff between ionic agents and electrolytes
ionic agents bigger than electrolytes
electrolytes are like sodium chloride and phosphates
moa of hydrophilic polymers
3rd class of flocculating agents eg acacia, tragacanth, alginates
low conc < 0.05% = bridging mechanism
high conc 1. protective colloid effect 0.05-0.1% polymer form protective coat aroudn the particle 2. viscosity enhancing effect >0/1% long molecules of polymer form network in the liquid = inc viscosoty = inc stability = red flowability
func of thickening agent an dmoa
- assist in suspension of solid particles
thru thickening of dispersion medium
eg - gums, gelatin, bentonite clay , carboxymethyl cellulose and polyvinylpyrollidone
effects depending on conc
flocculating effect if conc <0.05%
protective colloid effect 0.05-0.1%
viscosity enhancing effect if > 0.1%
notes for ph buffers in formulation
for optimal stability
but dont use unless rlly need
notes for preservaives
control microb contamination
cationic presrvatives not reco
notes for flavours, fragnants and colourants
could dec stability
large scale and small scale prep of suspensions
small
- mix solid drug w wetting agent in motar
- add small pop of liquid vehicle w additives to produce pourable micture
- transfer mixture to a measuring cylinder and make up required vol with remaining liquid vehicle
large
- add wetting agent to the solid drug in mixer
- add vehicle containing additives
- transfer mixture to high shear equipment to produce good dispersion
( avoid excessive shearing )
describe the precipitation technique of producign suspension
2
- organic solvent precipitation
water-insoluble drug dissolved in water-misicble organic solvent and then added to distilled water under standard conditions - ph induced precipitation
only applicable to drugs if solubility affected by ph
how to evaluate stability of suspension
2 methods
(1) transfer freshly prepared suspension to measuring cylinder and determine vol of sediment @ different time intervals
F = Vt /Vo
index of stability = vol of sedimen @ time t / initial vol of total suspension
and vol is proportional to height
F = 1 @ time t=0 , over time F < 1
DRAW THE PLOT , more deviation from 1 = less stable
(2) testing redispersibiliyt
- put suspensiona side for dispersed phase to settle down
- use mechanical device to shake
- determine number of shakes needed to redisperse the sediment
- ease of redispersibility inversely prop to number of shakes
