Part 1 Flashcards
define a coarse dispersion
a two-phase system in which one phase is distributed as particles or droplets in the continuous phase
how are dispersed systems classified?
by particle size
what is the range of particle size for coarse dispersions?
greater than 0.5 micrometers
can coarse dispersions be visualized under a microscope?
do they past through filter paper?
are they able to dialyze through a semi permeable membrane?
-coarse dispersion particles ARE visible under a microscope
-they do not pass through normal filter paper
-they do not dialyze through a semipermeable membrane
do particles in a coarse dispersion diffuse?
NO
give 4 examples of coarse dispersions
-pharmaceutical emulsions
-pharmaceutical suspensions
-red blood cells
-grains of sand
name the classes of dispersed systems by particle size, and state their particle size range
molecular dispersion - less than 1 nanometer
colloidal dispersion – 1 nm-0.5 micrometers
coarse dispersion - greater than 0.5 micrometers
give 3 examples of molecular dispersions
oxygen molecules
ordinary ions
glucose
give 2 examples of colloidal dispersions
colloidal silver sols
natural and synthetic polymers
explain the properties of molecular dispersions.
include:
-can they be seen under a microscope
-do they pass through filter paper
-do they pass through a semipermeable membrane
-do they diffuse
-particles are visible in ELECTRON microscope
-they pass through ultra filter paper
-they pass through a semipermeable membrane
-they undergo rapid diffusion
-
explain the properties of colloidal dispersions.
include:
-can they be seen under a microscope
-do they pass through filter paper
-do they pass through a semipermeable membrane
-do they diffuse
-CANNOT be seen by an ordinary microscope, but may be seen under ultra. VISIBLE in electron microscope
-pass through filter paper
-DO NOT pass through semipermeable membrane
-diffuse very slowly
define a pharmaceutical suspension
a COARSE DISPERSION containing finely divided INSOLUBLE material suspended in a liquid medium
name 7 applications of pharmaceutical suspensions
-parenteral (IM or SUBQ)
-oral
-aerosol
-soft gelatin capsules
-high solid pastes
-cosmetic lotions
-topical suspensions
are lotions liquid in liquid?
either solid in liquid or liquid in liquid. not clearly defined
what is the size of a human red blood cell
around 8 micrometers
true or false
suspensions can be given IV under certain circumstances
FALSE – cannot be given IV because the particle size is greater than the size of an RBC.
suspensions can only be injected IM and SUBQ
give 5 examples of parenteral suspensions (that can only be given IM/SUBQ)
-insulin zinc suspension
-sterile epinephrine oil suspension
-diphtheria/tetanus toxoids
-pertussis vaccine
-sterile benzathine penicillin G suspension
what is an advantage of suspensions being given parenterally? (IM/SUBQ)
this can be utilized to control the dissolution rate to prolong the effects
for example, 1 injection of Sterile Benzathine Penicillin G suspension can last a full course of antibiotics
also Insulin Zinc suspension can be utilized in a similar way to control the plasma profile
give 4 reasons for oral suspensions
-flexibility in dosing
-possible to make a palatable dosage form
-when liquid is preferred over solid bc easier to swallow
-certain drugs are chemically unstable in solution but STABLE when suspended as a small solid particle
as mentioned, one of the reasons for oral suspensions is the possibility to make a palatable dosage form.
give an example of this
chloramphenicol solution has a bitter taste.
however, chloramphenicol palimitate SUSPENSION has no objectionable taste bc the drug is insoluble in water and imparts no taste
name 3 major concerns of pharmaceutical suspensions.
which is the biggest concern?
-preventing caking of the particles
-ensuring adequate dispersion of the particles in the vehicle
-minimizing settling of the dispersed particles
PREVENTING CAKING IS MOST IMPORTANT
name 7 features desired for pharmaceutical suspensions
-therapeutic efficacy
-chemical stability (of all components)
-permanency of the preparation
-aesthetic appeal
-should settle SLOWLY and readily redisperse upon gentle shaking
-particle size should remain fairly constant over the shelf life
-should pour readily and evenly from container
what are 2 methods to aid in the dispersion step in preparing suspensions?
high shearing action (colloid mill)
surfactants
what is the goal of the dispersion step in preparing suspensions? name 2 results
to overcome the particle-particle attractive forces
results in removal of surface air and reduction of clumping of the particles
the process of dispersion creates a tremendous increase in what?
interfacial area between the dispersed particles and the dispersion medium
as mentioned, the process of dispersion creates a tremendous increase in the interfacial area between the dispersed particles and the dispersion medium.
what does this cause?
the surface free energy increases with increasing surface area when the particle size is reduced
when particle size is ______, the system becomes unstable and the particles want to aggregate
reduced
what is “W”
surface free energy
the _______ delta W, the more thermodynamically stable is the suspension of particles
SMALLER
How can delta W (surface free energy) be reduced?
is reducing surface free energy desirable?
by the addition of a wetting agent (HLB 7-9) (surfactant)
it is desirable to reduce surface free energy because the suspension of particles will be more thermodynamically stable.
after wetting, the particles will remain dispersed and settle relatively slowly
what is “surface electrical potential”
zeta potential
at what zeta potential does the repulsive force EXCEED the attractive van der waals forces? what does this mean?
when zeta potential is relatively high (25mV or more)
the particles are dispersed (separated) and are deflocculated
explain the circumstances in which flocculation would occur
when the zeta potential is reduced below a certain value by the addition of a PREFERENTIALLY ADSORBED ION – this charge must be opposite in sign to the particles.
the attractive forces will exceed the repulsive forces. Thus, the particles approach each other more closely and form loose aggregates (flocs)
what happens when zeta potential is above 25mV
the system remains deflocculated because repulsion energy is too high
true or false
flocculated particles exist as separate entities
FALSE
deflocculated particles
for deflocculated particles the rate of sedimentation is _____
LOW
the particle size is small and each particle settles separately
in which type of suspension is the sedimentation rate high – flocculated or deflocculated
flocculated because the particles are aggregated and thus larger and have more density
in which suspension is sediment formed rapidly? is this a bad thing?
(flocculated or deflocculated)
sediment is formed rapidly in flocculated suspension.
however, the sediment is loosely packed and easily redispersible so it isn’t a bad thing
what is “supernatant”
the clear liquid at the top of a suspension with no drug
what is the appearance of the supernatant in a flocculated suspension? what about deflocculated?
in a deflocculated suspension, the supernatant has a pleasing appearance and remains cloudy
in a flocculated suspension, the supernatant region is CLEAR
once a deflocculated suspension has formed a cake, is there any way for the patient to redisperse it?
NO
true or false
deflocculated suspensions cannot be sold to the patient
FALSE – they can, they just need to be used before the hard cake is formed
true or false
sediment is formed rapidly in a flocculated suspension
true
formed rapidly but it’s easily redispersed
give stokes law.
what does stoke’s law measure?
Stoke’s law measures sedimentation rate
v = 2r^2 (p-po)g / 9no
v = velocity of sedimentation of spherical particles
r = radius of spherical particles
p = density of spherical particles
po = density of medium
g = constant (acceleration due to gravity)
no = viscosity of medium
are there any exceptions to stokes law?
YES – wall effect + not all particles are spherical
wall effect - the settling velocity is sometimes less than the theoretical value
-not all particles are spherical. non spherical particles will settle more slowly. spheres have the minimum surface per volume
which settle quicker – spherical or non-spherical particles? why?
spherical particles settle quicker because they have the minimum surface per unit volume
in general - which pharmaceutical suspensions follow Stokes’ Law?
pharmaceutical suspensions containing LESS THAN 2% SOLIDS
give the formula for sedimentation volume
F = Vu/Vo
Vu = volume of sediment
Vo = total volume of suspension
which will have a higher value for sedimentation volume – flocculated or deflocculated suspensions?
flucculated ? will have a higher value
what does F stand for
sedimentation volume
what is the formula for degree of flocculation
B = F/F infinity
F = sedimentation volume of the flocculated suspension
F infinity = sedimentation volume of the suspension when deflocculated
if F is less than 1, what can you say about the relative volumes of the sediment and original volume of suspension?
the ultimate volume of sediment is SMALLER then the original volume of suspension
if the F value for a flocculated suspension is 1, what does this indicate about the supernatant region
upon standing, the supernatant region will NOT be clear
is it possible for F value to be greater than 1? explain
yes
this happens when the flocs formed in the suspension are so loose and fluffy that the volume they can make up is GREATER than the original volume of the suspension and thus additional vehicle is added
which is a more useful parameter for the degree of flocculation - sedimentation volume (F) or degree of flocculation? (B)
WHY
degree of flocculation (B)
B = F/F infinity
F = sedimentation volume of the flocculated suspension
F infinity = sedimentation volume of deflocculated suspension
more useful bc it relates the volume of the flocculated sediment to that in a deflocculated system
a typical flocculated suspension has an F value of what?
1
no clear supernatant region is observed
_____ are commonly used for the dispersion to have MAXIMUM EFFICACY
surfactants (HLB 7-9) – WETTING AGENT
___ and ___ may be used in the initial stage of preparation of suspension to disperse the particles.
what is the term for this?
ALCOHOL AND GLYCERIN
levigating agent
if we use a levigating agent such as alcohol or glycerin, is a wetting agent needed as well?
NO
the force of the mortar and pestle will get rid of the entrapped air and also reduce the particle size
what agent(s) are used to promote the dispersion of particles in the preparation of suspensions
levigating agents and wetting agents
define “structured vehicles”
an aqueous solution of polymeric material that is used as a dispersion medium
this polymeric material is usually negatively charged, hydrophilic colloid (bc we usually use water as a vehicle)
as mentioned, a structured vehicle is an aqueous solution of polymeric material.
give specific examples of these polymers (6). what else can they be used as?
methylcellulose
carboxymethylcellulose
Carbopol
acacia
veegum
tragacanth
also used as suspending agents – added to dispersed medium
how is controlled flocculation accomplished?
prepare the deflocculated, wetted dispersion of particles. bring about flocculation by adding a flocculating agent (such as electrolytes, polymers, and surfactants)
name 3 potential flocculating agents
electrolytes, polymers, and surfactans
what is the 1st step in the preparation of suspensions once you have the API particles (assumed already in the ideal size range)
once you have the API particles, add a wetting agent and dispersion medium (assuming the particles are already in the ideal size range)
once a wetting agent and dispersion medium are added to the API particles, what happens next in the preparation of suspensions?
-incorporating a structured vehicle will form a “DEFLOCCULATED SUSPENSION IN STRUCTURED VEHICLE” as the final product
-incorporating a FLOCCULATING AGENT will form a “flocculated suspension” as a final product
-incorporating a flocculating agent AND a structured vehicle will form a “FLOCCULATED SUSPENSION IN A STRUCTURED VEHICLE” as a final product
name the 4 potential products that can be formed in the preparation of suspensions.
which do we try to make the most and why?
-Uniform dispersion of deflocculated particles (API + wetting agent + dispersion medium)
-deflocculated suspension in structured vehicle
-flocculated suspension
-flocculated suspension in structured vehicle
flocculated suspension in structured vehicle has a very high expiration date, but the cost to make is much higher than the other 2. therefore, we try to make the other 2 when possible
of the 3 potential products in the preparation of suspensions, which has the shortest expiration and why?
deflocculated suspension in structured vehicle has the shortest expiration. This is because it will cake eventually and NOT be able to be redispersed
true or false
the uniform dispersion of deflocculated particles that is initially formed in the preparation of suspensions is NOT A PRODUCT
false – it is
we can dispense this as a product if the densities of the medium and the drug are very close to each other because the sedimentation rate will be very slow.
however, this case is very rare
true or false
a wetting agent can also be a surfactant
true
how many different types of potential products can be formed in the preparation of suspensions?
4
-uniform dispersion of deflocculated particles
-deflocculated suspension in structured vehicle
-flocculated suspension (in the dispersion medium only (water))
-flocculated suspension in structured vehicle
which has higher (longer) expiry -
-deflocculated suspension in structured vehicle
-flocculated suspension
flocculated suspension
flocculated suspension in a structured vehicle is a potential final product in the preparation of suspensions.
how is this formed?
-dispersing the particles, add a flocculating agent, add a LYOPHILIC POLYMER to form a structured vehicle
name 3 commercially available vehicles for suspensions and differentiate them
ora sweet = syrup vehicle. CLEAR
suspendol-S = compounding vehicle. not as clear as ora sweet.
Ora-plus = oral suspensing vehicle. most cloudy
in the manufacturing industry, what suspensions are usually made?
what about in compounding?
manufacturers usually use “flocculated suspension” and “flocculated suspension in structured vehicle”
compounding = deflocculated suspension in structured vehicle. this is bc we normally don’t need an expiration greater than 2 weeks
what is the range of zeta potential for “noncaking zone”
+25mV to -25mV
anything above 25mV or lower than -25mV will form a cake because the repulsion energy is too high (either negatively or positvely)
which has smaller sediment volume - flocculated or deflocculated
deflocculated. forms tightly compact, small cake
the “noncaking zone” is also known as __ __
controlled flocculation
as the concentration of KH2PO4 increases, what happens to zeta potential?
KH2PO4 is an electrolyte - flocculating agent
as the concentration increases, zeta potential decreases and even goes negative
when zeta potential is very high, is the system flocculated or deflocculated?
the sedimentation is __ and ___
deflocculated
slow and small (cake)
what is KH2PO4
monopotassium phosphate.
an electrolyte used as a flocculating agent
when zeta potential is going from 100mV to 25mV, what is happening to sedimentation volume? (F)
what happens once zeta potential reaches 25mV to -25mV?
it increases
once zeta potential reaches the noncaking zone, sedimentation volume does not drastically change - remains steady
once zeta potential reaches below -25mV (with the continual addition of KH2PO4), what happens to sedimentation volume(F)?
while it was steady in the noncaking zone (flocculation time) it begins to decrease once below -25mV is reached
what can tragacanth be used as
a suspensing agent
what can sodium alginate be used as
a suspending agent
can glycerin be used as a suspending agent?
yes
name 4 suspending agents that were analyzed in a Stormer viscometer
glycerin
cmc
tragacanth
sodium alginate
what does a Stormer viscometer measure?
viscosity
of the 4 suspending agents analyzed in the modified Stormer viscometer, which was the only one to express a linear relationship?
what does this mean?
glycerin
its viscosity is suitable for suspending agents but it is TOO HIGH to be able to pour easily. it is also too sticky
explain the desirable properties of a suspending agent for suspensions.
how is this visualized?
Ferranti-Shirley coneplate viscometer
a suspension should have high viscosity at negligible sheer (during storage) and should have a low viscosity at high shearing rates (so it can be poured)
what is “thixotrophy?”
what suspending agents have this? is this a desirable quality?
viscous under static conditions but will flow over time when shaken
5% micro bentonite
5% veegum
50:50 CMC and micro bentonite
yes, it is desirable quality
which will have a faster dissolution rate – particles with rough surfaces or particles with smooth surfaces?
rough surfaces will have higher dissolution rate due to capillary action
