chp3 diffusion Flashcards
what is diffusion?
is the process of mass transfer of
individual molecules of a substance brought about by
random molecular motion and associated with a
driving force such concentration gradient.
give examples on diffusion in pharmaceutical sciences
1, drug release from tablets, capsules, ointments and suppository bases
2.drug absorption and elimination
- permeation and distribution of drug molecules
- osmosis and dialysis
what is osmosis?
involves the passage of a solvent only through a semipermeable membrane.
what is dialysis?
involves the passage of solvent and solute through a membrane
give an example on the osmotic drug release system
release systems that use osmotic pressure to control the delivery of drugs aka “osmotic pumps”.
example: Oros technology used in Pfizer
Procardia XL
what is the difference between procardia and procardia XL?
About a four-fold lower fluctuation
index (ratio of peak to trough) was
observed with once daily
PROCARDIA XL® than conventional
immediate-release PROCARDIA ®
capsule at t.i.d. dosing
- minimizing adverse effects
- improved patient compliance
The label indication for PROCARDIA
XL® was expanded to include
treatment of both angina and
hypertension.
both have the same active ingredient: Nifedipine
the passage of matter through a solid barrier (polymeric membrane) can occur by?
• Simple molecular diffusion or permeation through
nonporous media: it depends on the solubility of
the permeating molecules in the bulk membrane
• Movement through solvent-filled pores and
channels: it is influenced by the relative size of the
penetrating molecules and the diameter and shape
of the pores
both require dissolution first
what causes diffusion? is it slow? does the slow rate matter?
Diffusion is caused by random
molecular motion therefore, it is a slow process.
• The diffusion rate of a molecule is estimated to be:
– In gases = 10 cm/minute
– in liquids = 0.05 cm/minute
– In solids = 0.0001 cm/minute
• Is that slow process significant? The answer is yes.
Because the thickness of cell membrane is 5 nm
(0.0000005 cm) it will take a molecule a fraction of a
second to cross that thickness.
give an example on a drug that we need the slow diffusion rate for
levonorgestrel-releasing implants
(Norplant®): a contraceptive approved
for 5 years of continuous use in
human. It provides 40 – 50 g/day in
the first year that decreases to 25 – 30
g/day in the fifth year.
how can the mixing of the drug in solution with intestinal contact effects the diffusion
– At first glance, mixing appears to be a simple
process; however, several molecular- and
macroscopic-level processes must occur in
parallel for efficient mixing to occur.
– It is important to remember that diffusion
depends on random molecular motions that
take place over small molecular distances
“microscopic phenomenon”
give some examples on these macroscopic processes
convection,dispersion, and stirring.
remember that diffusion is kinetic and needs the equilibrium to not be balanced in order to occur
ok
what are the different diffusion driving forces
1.Concentration:
– Passive diffusion in absorption
– Drug dissolution
- Pressure:
– Osmotic drug release - Temperature:
– Lyophilization - Electrical potential:
– Iontophoretic dermal drug delivery
– Electrophoresis
what is fick’s first law of diffusion
J= (d * M) \ A . dt
it then becomes
J= -D* (dC\dX)
Where
D: the diffusion coefficient of a penetrant (also called the diffusant) in cm2/sec
C: concentration in g/cm3
X: the distance in cm of movement perpendicular to the surface of the barrier
the negative sign is for the direction. the flux is always positive
J is g\sec
if dC\dX is 0 the diffusion stops
what is D the diffusion coefficient affected by?
– Concentration
– Temperature
– Pressure
– Solvent properties
– Chemical nature of the diffusant
what is the sink condition?
It is obtained when the solution in the receiver compartment is constantly removed and replaced with fresh solvent to keep the concentration in the receiver compartment at a low level.
• Sink condition has biological relevance to the absorption process in the GIT.
what is the difference between a barrier and a membrane ?
Membrane: it is a biological or physical film
separating two phases, and materials pass by
passive, active, or facilitated transport across this film
– Barrier: it applies in a more general sense to the
region or regions that offer resistance to passage of
diffusing material, the total barrier being the sum of
individual resistance
what is the law of flux in the case of sink conditions
J= P A C
where p is the permeability
A is the membarne and C is the conc.
what is the law of permeability? aka the permeability coefficient
P= (D.K)\h
or from the law M= PACt
– A: the surface area through which diffusion occur.
– Cd
: concentration in the donor phase.
– M: the amount of permeant (drug) in the receiving
sink.
how can we measure the permeability in early drug development
permeability through monolayers of Caco-2
cells are usually measured.
– Derived from human colon adenocarcinoma.
– Form monolayers that have remarkable morphological
and biochemical similarity to the small intestinal
columnar epithelium.
– Used as a vitro model for the study of drug
absorption and metabolism during absorption in the
intestinal mucosa
give an example on multilayer diffusion
Membrane permeation studies using Caco-2 cell
monolayers on permeable supports such as
polycarbonate filters
also the skin surface
what is the permeability law for multilayer diffusion
p= ( Dm K Da)\ ( hm Da+ 2ha Dm K)
hm: the thickness of the polymer membrane
– ha: the thickness of the stagnant aqueous diffusion
layer
– Dm: the diffusifity of the drug in the polymer
membrane.
– Da: the diffusifity of the drug in the stagnant aqueous
diffusion layer
– K: the partition coefficient
note that The flux J through this three-ply (mulitilayer diffusion) barrier is simply
equal to the permeability, P, multiplied by the
concentration gradient (Cs-Co)
what is the influx law for sink conditions multilayer diffusion
J= (Dm K Da Cd)\ (hm Da+ 2ha Dm K)
Remember that:
– The higher the degree of stirring the thinner
is the stagnant aqueous diffusion layer
– The slower the stirring, the thicker is this
aqueous layer
ok
Depending on the properties of the diffusing drug, two
cases can be considered mention them
- The membrane will control drug release
membrane control
– Generally for hydrophilic drugs - The stagnant aqueous layer will control drug
release solvent layer control
– Generally for hydrophobic drugs
what is the permeability law for membrane control multilayered sink conditions
drug permeability
through the polymer membrane will be «< than
through the solvent layer
The term 2haDmK can be neglected
J= Dm K Cs\ hm
what is zero order release
– It is the ideal type of release.
– In zero order release, the amount released is
a function of time only in other words, the
concentration is constant.
– How can we keep the concentration constant?
by using a saturated solution in the
presence of excess solid drug the
concentration will equal the solubility at all
times till the excess solid drug is
consumed.
what is the lag time
it is the time required for the diffusant to establish a uniform conc. gradient within the membrane separating the doner from the receiver
