Lecture 13/14 Flashcards
liquid dosage forms - suspension (2/20, 2/22)
suspensions
liquid preparations that consist of solid particles dispersed throughout a liquid phase in which the particles are not soluble
example - pepto bismol
bismuth subsalicylate
active ingredient in pepto bismol
insoluble salt of salicylic acid linked to bismuth cation
suspension vs solution - chemical stability
solution - first order (log graph)
suspension - zero order (constant graph)
suspension vs solution?
due to solubility, chemical stability, and taste (oral suspension of erythromycin takes better than solution)
less excretion by suspension
suspension vs tablets?
due to flexibility of dose, ease of swallowing, and faster dissolution rate
components of suspension
flocculating agent, structured vehicle system, and wetting agent – different
also - active ingredient, vehicle, buffer, preservative, antifoaming agent, and flavor/sweetener
desirable properties of suspensions
does not settle rapidly
not hard cake at the bottom from the particles
easy to administer (not too viscous or easily flowable through syringe)(fluid enough to spread over external area but not so mobile it slides off)
particle size remains constant during storage
settling
stoke’s law
measured in cm/sec
sulfadiazine in water - 54 seconds to settle 1cm
microcrystalline sulfadiazine - 90min to settle 1cm
sorbitol solution as vehicle for microcrystalline sulfadiazine - 17 days to settle 1 cm
stoke’s law equation
V (cm/sec, velocity of sedimentation)
d^2(diameter of particle in cm) x
Ps(density of solid) - Pl (density of liquid) x
980 (gravity constant)
/
18
n (viscosity of liquid)
particle size
1-50 mcm
micropulverization, fluid energy grinding, and spray drying
micropulverization
10 to 50 mcm
most oral and topical suspensions
high speed attrition or impact mills
fluid energy grinding
under 10 mcm
parenteral or ophthalmic suspensions
jet milling, micronizing
shearing action of high-velocity compressed airstreams on the particles in a confided space
spray drying
under 5 mcm
dryer – a cone-shaped apparatus into which a solution of a drug is sprayed and rapidly dried by a current of warm, dry air circulating in the cone
suspension formulation designs
dispersed phase (solid particles)
dispersion medium
types of suspensions
dispersed suspension
flocculated suspension
structured vehicle system
thermodynamic stability equation
change in G (increase in surface free energy)
Ys/l (interfacial tension between solid and liquid) x
change in A (increase in surface area)
thermodynamic stability
a suspension is stable when change of G is equal to 0
can never be reached in a suspesnion because we usually want small particles (high deltaA) for rapid dissolution
moves towards deltaG = 0 overtime due to processes that reduce deltaA
processes that reduce the surface area
aggregation and crystal growth (increases particle size)
Van der Waals attractive force
operates at moderate distance from the surface but becomes very strong close to the surface
formulation factors do not affect it
hydration repulsive force
due to adsorbed water molecules at the surface of a particle
formulation factors do not affect
electrostatic repulsive force
due to surface charge on the particles
could be controlled by the formulation
steric repulsive force
due to an adsorbed layer of neutral polymer at the surface of a particle
may be controlled by the formulation
repulsive force
+
comes closer to 0 from the top to the bottom
attractive force
-
comes closer to 0 from the bottom to the top
dispersed suspension
make repulsive forces dominant
particle repel each other and do not aggregate
problem - particles settle as individual particles leading to a cake sediment that can be difficult to resuspend
controlled flocculation
repulsive and attractive forces are in balance
particles are attracted to each other at the secondary minimum to form aggregates (known as floccules), which settle to produce a sediment with a high volume
easy to redisperse
settles fast, but less prone to compaction so breaks up easier
sediment volume (f)
= final volume of sediment / volume of suspension
degree of flocculation (b)
= sediment volume of test suspension / sediment volume of dispersed suspension
flocculating agents
clay (diluted bentonite magma) – oral suspension
alteration in the pH of the suspension – parenteral solution
electrolytes – reduce the electrical barrier between the particles
non-ionic or ionic surface-active agents
suspension settles too rapidly
hinders accurate measurement of dosage
esthetically not good
structured vehicle
thicken the dispersion medium and help suspend particles
should not interfere with availability of the drug
should not make the suspension too viscous to agitate or to pour
examples - polymer and clay
rheology
study of flow characteristics
shear rate (dv/dr) – difference of velocity (dv) between two planes of liquid separated by a distance (dr)
shear stress (F) – the force per unit area, F’/A, required to bring about the flow
newtonian vs non-newtonian flow
non-newtonian flow
plastic - not fully exponential or constant (mix)
pseudoplastic – exponential
dilatant – logarithmic graph
newtonian flow
F = F’/A = visocity(shear rate)
plastic non-newtonian flow
typical of flocculated suspensions
f (yield value) - threshold of shear stress necessary to initiate flow, represent the strength of the attractive force of the secondary minimum
shear-thinning
pseudoplastic
typical of polymer solutions such as methyl cellulose, etc
shear-thinning
dilatant
exhibited by suspension having a high solids content
shear-thickening
thixtropy
the ability of a system that was disturbed by an applied shear stress to return to its undisturbed structure
plastic and pseudoplastic (shear thinning) fluids show it
at rest, a gel will stabilize the suspension
dispersed suspension approach
aim to achieve very slow rate of sedimentation
cloudy suspension
dense sediment
may form non-suspendable sediment
stoke’s law
controlled flocculation approach
rapid rate of sedimentation
clear supernatant
large sediment volume
easily redispersed by shaking
structured vehicle approach
may appear as a semi-solid when undisturbed but is fluid when shaken
no sedimentation
thixotropic
wetting
displacement of air from the surface of a particle by the vehicle
consider water-based (aqueous) vehicle
consider hydrophilicity (like water) or hydrophobicity (dislike water) of the drug particles
contact angle
a high contact angle indicates poor spreading and that cohesive forces of the liquid is strong
hydrophilic - less than 90 degrees
hydrophobic - greater than 90 degrees
wetting agent
surface-active agent added to reduce the surface tension
example - tween 80
used when the particles float as a result of pores filled with air not water
