Anyone who has ever tried to give a 5-year-old an antibiotic can appreciate where Edward M. Rudnic is coming from.

As the founder of Advancis Pharmaceutical Corp. in Germantown, one of his goals is to take amoxicillin and convert it to a taste-free powder that could be sprinkled on anything - even ice cream - and tots would be none the wiser.

 

His plans are not quite a reality yet, having run into a snag in clinical testing, but Rudnic hasn't stopped trying. And he is not alone.

Ever since there were drugs, science has looked for ways to improve their delivery to better satisfy doctors and patients. They've turned injections into pills, cut daily dosing amounts and enhanced flavors, hoping it would all add up to happier patients, safer medication and more profit.

But efforts have ramped up recently as advances in technology have made more things possible, and businesses have had to get increasingly creative to find a competitive edge.

It can take a dozen years and $1 billion to create a drug from scratch, which often means a long wait before new companies see any sales.

By taking proven drugs and repackaging them with new delivery systems, entrepreneurs can potentially cut years off the timeline and maybe millions off the price tag.

And along the way, they just might solve a problem that has vexed physicians for decades: People aren't very consistent when it comes to taking their meds.

Some patients are afraid of needles. Others forget to take their pills every four hours. And parents struggle with squirmy children who often hate to take any kind of medicine.

"A better delivery system is a clear way of remedying that, especially if you're talking about a patch or something that [doesn't require] remembering to open up a vial and take X number of pills," said Kenneth I. Kaitin, director of the Tuft's Center for the Study of Drug Development.

With that in mind, companies are developing patches that deliver Alzheimer's treatments and birth control hormones, edible strips that release cough medicine, lollipops that yield a pain reliever for cancer patients and nasal sprays that dispense insulin and anti-obesity drugs.

Diabetes treatments are a hot area, with many companies working on new ways to deliver insulin or check glucose levels. An associate professor at the University of Maryland Biotechnology Institute, for example, has invented a contact lens meant to measure blood sugar.

Elsewhere in Maryland, where biotechnology is considered a key industry, Baltimore's Guilford Pharmaceuticals (which was acquired by a Minnesota company last year) developed an implantable wafer that treats brain cancer.

And at least three Gaithersburg companies are working on unusual ways to deliver drugs: MedImmune Inc. has its inhaled FluMist vaccine, Iomai Corp. is creating vaccine patches, and Panacos Pharmaceuticals Inc. is working on an HIV pill meant to replace a current therapy that has to be injected.

The drug delivery field is among the fastest-growing areas in the pharmaceutical industry. Sales of medications with novel delivery systems are increasing by 15 percent every year, according to market analysts Scrip Reports. By 2009, the drug delivery products and services market is expected to top $67 billion - more than double the $24 billion figure of 2003 - says a study from analysts NanoMarkets.

But a new way of dispensing a drug does not always mean it's better for a patient. Businesses still need to show their replacement versions are as good as or better than the old to get Food and Drug Administration approval.

Norplant was developed as a contraceptive that could be implanted once and protect against pregnancy for five years - unlike birth control pills, which require daily dosing. But it was pulled from the U.S. market in 2000 after women developed serious side effects, including severe headaches and depression.

A similar, but ostensibly safer, birth control implant called Implanon was approved for sale last month.

And not all new versions are as well received as their counterparts. Relatively few people have picked MedImmune's nasal flu vaccine over the traditional shot. The company is working on a new formulation it hopes will sell better.

There are always risks in drug development, but that shouldn't stop the search for improvements, said Stanley C. Erck, president and chief executive of Iomai. His company's goal is no less than changing "the entire way vaccination is practiced."

 

Iomai was founded by a scientist at the Walter Reed Army Institute of Research, where he discovered that you could deliver proteins through the skin and stimulate a powerful response from the immune system.

That led to the 1997 formation of the company and its current portfolio of needle-avoiding vaccine patches: one to combat travelers' diarrhea, another to fight avian flu and a third to prevent seasonal flu. A fourth patch seeks to enhance the traditional flu shot, and perhaps cut the dosage level required to a tenth, possibly helping to eliminate the supply issues that have dogged the vaccine industry.
 

All of Iomai's patches are still in testing phases and none has yet made it to market, but Erck has high hopes.

"If we can show that we can replace the injectable influenza vaccine with a patch, it could be the basis for all vaccines," he said.

Aside from convenience, eliminating the needle could cut vaccination costs by also doing away with certain cumbersome storage requirements and the need for paid health care workers to administer the drugs.

Erck envisions a day when consumers could obtain vaccine patches at their local drugstores, wear them for a few hours at home, and be good to go.

At the Johns Hopkins University, researchers at the newly created Institute of NanoBioTechnology are using tiny particles to make drugs more efficient and multifunctional.

"Many of these approaches using nanotechnology are beginning to look like what people conceived several years ago as 'smart pills,'" said the institute's director, Peter C. Searson. In theory, nanoparticles could be added to drugs to help them target specific organs or types of cells. (Nanoparticles and other nano words derive from nanometer, a billionth of a meter.)

The goal at UPM Pharmaceuticals Inc. in Dundalk is to make medications that last longer than most. Scientists there are developing liquid blood pressure and pain medications that are easy to swallow and need only be taken once a day, unlike others.

"People are willing to pay for that convenience," said UPM Vice Chairman Harold Chappelear. "And the convenience is enormous, it really is."

Convenience was a key motivator for Rudnic when he was putting Advancis together in late 1999. Too many antibiotics have to be taken three and four times a day, and he thought he could do better, particularly with amoxicillin, a penicillin that's among the safest and most prescribed drugs available.

"There's a lot of companies out there that work on delivery systems," Rudnic said. "I think that the real value is to try to find the true unmet clinical need, where your innovation can quickly be transformed into successful medication."

Innovation in antibiotics has been typically focused on the molecule associated with it. Not much had been done with their delivery in years, until Rudnic's team decided it might be possible to deliver the drug in time-released bursts. That means one daily pill could replace multiple doses.

There was a lot of trial and error involved in the company's Amoxicillin Pulsys product, with both adult and pediatric versions failing in clinical trials. But earlier this month, Rudnic got the news he'd been waiting for.

A retrial of the drug in adults and adolescents showed it was a keeper, and the company plans to seek commercial approval from the FDA within six months.

A children's version of the drug, which was to have come in a tasteless "sprinkle" formula that could be added to food, has not fared so well. It stalled after failing in a midstage clinical trial, and Rudnic's team is still trying to figure out how to fix it.

They're also trying to come up with ways to adapt Pulsys technology to combat other infections.

Said Rudnic: "We're not done yet."