Sonicated transdermal drug transport – paper by Joshi and Raje, 2002

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 0 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 5.73 Nonlinear regression needed So if 0.4 < fR < 1, then Which means n = 0 long times 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