Ultrasound patch awaits transducer

November 4, 1992

Researchers want to improve on the transdermal drug delivery technologyused in nicotine patches by employing ultrasound to push drugsdeeper into the skin. But an ultrasound patch will remain a pipedream until super-high-frequency transducers are

Researchers want to improve on the transdermal drug delivery technologyused in nicotine patches by employing ultrasound to push drugsdeeper into the skin. But an ultrasound patch will remain a pipedream until super-high-frequency transducers are developed thatare small and rugged enough to make such a system practical.

The scientific basis for an ultrasound patch was studied byresearchers at the University of California at San Francisco,who found that applying ultrasound to the skin allows drugs topenetrate more quickly.

The researchers used transducers at frequencies of 2, 10 and16 MHz, and found that higher frequency transducers apply moreenergy near the surface of the skin and thus allow drugs to penetratethe body more efficiently, according to Richard Guy, a co-authorof the study.

In the second of two studies on the phenomenon, Guy and hiscolleagues used ultrasound waves to drive lanthanum hydroxide,a harmless chemical that normally does not penetrate the skin,into the deeper skin layers of hairless guinea pigs. Their studywas published in the August issue of Pharmaceutical Research.The previous study was published in the April issue of the journal.

Transdermal drug delivery has gained favor in products suchas nicotine patches because of its convenience and efficiency.Transdermal delivery circumvents the gastrointestinal tract, wherethe digestive process can often alter the effects and dosage levelsof drugs.

Administering a drug transdermally also improves patient compliancebecause putting on a patch is easier than taking pills every threeor four hours, Guy said.

Some drugs are not potent enough for transdermal delivery,however, and would require either chest-sized patches or an extraboost to penetrate the skin. That's where ultrasound could proveuseful, according to Guy.

"The idea behind (the ultrasound) approach is that youwould have a gizmo that you could use to pretreat your skin to`permeablize' it," Guy said. "Then you would apply thepatch, the drug would be delivered and the skin would recoverits natural state in some known period of time."

Ultrasound is being used by sports trainers to deliver anti-inflammatorydrugs such as hydrocortisone to knee injuries. But reaching alarger market for ultrasound drug delivery would require a systemthat could be used in the home.

Possible candidates for treatment with an ultrasound patchcould include skin disorders or joint pain. Drugs based on peptidessuch as growth factors could also be delivered transdermally.

A patent has been issued to the university for the techniqueand a Redwood City, CA-based nicotine-patch maker, Cygnus TherapeuticSystems, has acquired rights to commercialize the technology.

But research in ultrasound drug delivery has faltered becauseof the lack of a super-high-frequency transducer appropriate forthe home market.

"We're stalled at this point," said Guy. "(Weneed to) identify ways to get hold of higher frequency transducersto pursue the idea that the higher a frequency one uses, the moreenhancement one will see."

Examining the effects of a transducer in the range of 50 to100 MHz would be the next step in the research, to study whethersuch a transducer would be more effective and whether it wouldcause physiological changes in the skin, Guy said.

The researchers found that applying ultrasound for 20 minutesat 16 MHz produced some changes in skin cells--small "cavitations"or bubbles. The researchers don't know whether these changes areharmful or reversible, or if higher frequency transducers wouldincrease the effect.

The lack of an appropriate transducer has relegated ultrasounddrug delivery research to the back burner at Cygnus, accordingto director of research Russ Potts.

Cygnus makes Nicotrol, a nicotine patch marketed by the Parke-Davisdivision of Warner-Lambert. The company is working to expand patchtechnology to other drugs as well, but is also researching waysto move beyond passive patch systems to a more active approach.

Iontophoresis, or electrically enhanced drug delivery, currentlyconsumes the lion's share of research at Cygnus because that technologyuses off-the-shelf components and thus appears easier to commercialize,according to Potts.

That could change with the development of a transducer thatis small, cheap and rugged enough to make transdermal ultrasounddrug delivery practical.

"To get to commercial reality, it needs to be more affordable,much easier to use and not have to be used in a doctor's office,"Potts said. "To get it to that next step is going to requiresome other technology or some advancement of the current technology."