1. Sonicated transdermal drug transport – paper by Joshi and Raje, 2002
Sonophoresis is defined as the use of ultrasound to increase the
movement of drugs across living skin, underlying phenomena:
1. cavitation, the generation, oscillation, and breaking of tiny
gas bubbles
2. thermal effects, T goes up, shown though to be negligible
3. induces convection transport, but not by much
4. mechanical effects due to stresses caused as a result of
P variations, negligible effect

2. Slope is the transport rate
Cavitation plays a key role
For initial 4 hours there
is a 13 fold increase in
the transport flux
2. After that the flux becomes
the regardless of whether
sonication is used
3. Ultrasound degasses the
the skin hence no more
cavitation to the facilitate
the drug transport
4. Cavitation proportional to
1/f
5. Common conditions used
are f = 1-3 MHz and
intensity 0 – 2 W/cm2

4. The sonophoretic enhancement of transdermal drug transport can
be qunatitatively predicted based on the knowledge of the drug’s
passive skin permeability (PSC) and the octanol-water partition coefficient
Ko/w, using the following equation
If e >1 there is a sonophoretic enhancement to the drug’s transport,
and if e <1 then no effect
In general drugs that passively diffuse through the skin at a slow rate
are the ones most enhanced by the application of ultrasound

5. Joshi & Raje
paper discussing
overall PK
method.
amount of time, effort, and experimental material.

6. Other methods for enhancing transport of drugs across skin
Chemical enhancers, increase transport by
a. increasing the drug solubility
b. increasing the partioning into the SC
c. fluidization of the lipid bilayers
d. disruption of intracellular proteins
e. can also use a combination of different chemicals
2. electroporation, creates a transient high permeability state as
a result of the application of high voltage for a short period of
time, can also be combined with chemical enhancers and
ultrasound

7. More fascinating quotes from Joshi
and Raje’s article

8. Krewson et al. 1995 in Brain Research published an interesting
study on an implantable device to release NGF for treatment of
neurological disorders like Alzheimer’s, BBB will not allow transport
of systemic drugs like NGF
They wanted to quantify the transport of NGF within the brain interstitium
So they implanted CR polymeric disks with NGF into the brains of
adult male rats
They measured the spatial distribution of NGF in brain tissue slices
surrounding the implants for up to 1 week, they used NGF, [125I]NGF
and used ELISA, radiation counters, and autoradiography
Some definitions if you read the paper:
ipsilateral means the same side
rostal means a structure located closer to the head or higher
than another
caudal means closer to the feet or lower
O O
Coronal section

12. OCUSERT PILO 40, a contact lens like material designed to
continually release pilocarpine following placement in the cul-de-sac
of the eye, produces pupillary constriction and increases aqueous
humor outflow decreasing intraocular pressure, wear it for one week,
treats glaucoma
.5 mm thick
5.5 mm diameter
Basically a thin disk so one
could use model shown in
Section 5.6.1
13 mm

14. People have also proposed approximate solutions for the fraction release
that makes it somewhat easier to analyze data, so rather than use
Equation 5.80
Nonlinear regression needed
So if 0.4 < fR < 1, then
long times
Which means n = 0
So take your data and define X = 1 - fR
Slope provides De

15. If fR < 0.4, then
Slope gives De
From the Bawa paper