exam 1 lecture 3 Flashcards
suspensions
liquid preparations that consist of solid particles in liquid phase
suspensions vs solutions
reasons for suspensions
solubility
chemical stability –> solution: first order, suspension: zero order
palatability –> erythromycin estolate oral suspension more palatable than solution
suspensions vs tabs
reasons for suspensions
flexibility of dose
ease of swallowing
dissolution rate
components of suspension
API
vehicle
buffer
preservative
flocculating agent
structured vehicle system
wetting agent
antifoaming agent
flavor + sweetener
desirable properties
suspended material should not settle rapidly
particles that settle should not form hard cake, but be able to redisperse
ease of administration: not too viscous for pouring. lotions should be fluid enough to disperse
particle size remain constant during storage
stokes law
V = (d^2 * (ps-pl) * 980) / (18*n)
particle size
1-50 um
micropulverization: high speed attrition or impact mills (topical + oral 10-50 um)
fluid energy grinding: shearing action of high velocity compressed airstrear (<10um, parenteral + ophthalmic)
spray drying: solution is sprayed and rapidly dried by air. (< 5um)
bring ∆G to zero
reduce surface area (∆A) + increase particle size
aggregation
crystal growth
van der waals attactive force
operates moderate distance from surface but becomes very strong close to surface
formulation factors do not effect
hydration repulsive force
due to absorbed water molecules at surface of a particle
formulation factors do not affect
electrostatic repulsive force
surface charge on particles
may be controlled by formulation
steric repulsive force
due to absorbed layer of neutral polymer at surface of particle
may be controlled by formulation
dispersed suspension
make repulsive force dominant
particles do repel eachother and do not aggregate
problem: particles settle and can lead to cake
controlled flocculation
repulsive + attractive force in balance
particles attracted to each other at secondary minimum to form aggregates (floccules)
floccules settle to produce a sediment w/ high volume
this sediment is easy to disperse
dispersion
settles to form compact cake that is difficult to break up
flocculation
settles fast but less prone to compaction, breaks up easily
sediment volume (F)
volume of sediment / volume of suspension
degree of flocculation
sediment volume of test suspension / sediment volume of dispersed suspension
flocculating agents
clay - oral suspension
alteration in pH of suspension - parenteral solution
electrolytes - reduce barrier between particles
non-ionic or ionic surface-active agents
structured vehicle system
semi-solid when undisturbed, but fluid when shaken
thicken dispersion medium and help suspend particles
- polymer: CMC, methylcellulose, microcrystalline cellulose, xanthan gum
- clay: bentonite, magnesium aluminum sillicate
should not interfere with availability of drug
should not make suspension too viscous to agitate or pour
rheology
study of flow characteristics
shear rate - difference in velocity between two plans of liquid seperated by distance (dr)
shear stress - harder the stress, quicker the liquid flows
newtonian flow
linear relationship between shear stress and rate of shear
non-newtonian flow
non-linear relationship between shear stress and shear rate
plastic
pseudoplastic
dilatant
plastic
flocculating suspensions
needs threshold to initiate flow
“shear thinning”
psuedoplastic
CMC, methylcellulose
needs a lesser threshold to flow
latex paint
dilatant
shear thickening
higher the force, less flow
cornstarch + water
wetting
wet particle to remove air from surface of a particle by vehicle
wetting agent
if solid has rough surface with many small pore, aqueous vehicle may not be able to enter the pores
best solution is to reduce surface tension
use surfactant like polysorbate 80
