POSTED 10 OCT 2002

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An old Norwich Pharmaceutical (then owners of Pepto-Bismol) ad circa 1948. More old-time commercials (print and soundbytes) can be seen at Danny Goodwin's historical commercials. Courtesy Lou Genco's Old-Time Radio site, Pepto-Bismol ©Proctor & Gamble.

The computerized stomach. The virtual tablet ("Heavy pill" image) is denser than stomach fluid, so it quickly sinks, then gets pushed by the stomach wall toward the pylorus and small intestine . A new contraction wave starts every 20 seconds in the middle of the stomach. These waves are the major cause of mixing in the stomach

In the "Floating pill" image, a "floater" tablet stays out of the contraction zone. Legend: red circle= tablet, pink=drug dispersion, arrows= fluid movement. James Brasseur and Anupam Pal, Penn State.

To answer the question, a group at Penn State has turned to the computer. No, they haven't started pouring long-acting Alka-Seltzer into the number-cruncher. Instead, they have used magnetic resonance (MRI) scans and pressure measurements of real, live human stomachs to cook up a virtual stomach inside a computer.

Before you give a belly laugh and move on, consider that the details of how long-acting pills break down and release meds are something like a gastrointestinal black hole.

Got a belly-ful
It turns out that, in some conditions, meds are released too quickly, in others, too slowly. The release rate depends on where the pill rests in the stomach, the intensity of stomach contractions, and the opening and closing of the pylorus, the valve that feeds the small intestine.

Using the virtual stomach, James Brasseur, professor of mechanical engineering and project leader, says, "We can simulate the tablet breaking down with our new approach, watch the slow release of medication happen in a computer movie and analyze the process. Computer simulation allows us to control the stomach and therefore provides more detail than you could get with human or even animal experiments." See the computer movie(4.7MB)

But there's more. "Computer simulation," he contends, "may be the only way to observe the stomach's mechanical processes in such fine detail."

Taking a powder
The simulations show that placement is key to the fate of a long-acting pill. The first image below shows a heavier-than-stomach-fluid pill dropping to the bottom and getting trapped in the contraction zone near the small intestine.

Here, pills quickly get broken apart, Brasseur says. "Contraction waves are the main event that creates the mixing and breaks down the tablet. If it moves into that region, it will break down much faster."

Conversely, if the pill floats, as shown in the 2nd image above, it may not reach the contraction zone until the stomach is almost empty. Then, says Brasseur, "You will get a sudden release, or the tablet will get pushed out with the last remnants of food, and you'll get pieces of tablet moving down the small intestine" -- not what the drug companies want at all.

Can't stomach it?
The virtual stomach could also be used to investigate diseases like gastroparesis and hyperactive stomach, where the stomach releases its contents at the wrong rate. If the release is too fast, nutrients enter the small intestine too rapidly to be digested. If it's too slow, "you will feel bloated and uncomfortable," Brasseur says.

Stomach contractions, he adds, are part of a reflex system. Receptors in the small intestine observe how much nutrient is passing through the wall and signal the stomach to adjust the contractions and pyloric valve accordingly. "If this reflex is broken down, the stomach will release its contents too quickly or too slowly," Brasseur says.

Anupam Pal, a postdoctoral researcher, contributed to the modeling effort, which was supported by a drug company.

The virtual gut could be used to design pills for specific situations, since drug dispersal in the stomach depends on what you've been eating, your stress level and other drugs you are taking. Says Brasseur, "Once we understand enough about that, it will affect the delivery mechanism that a drug company can use. You can change the weight or specific gravity according to what the person has been eating."

-- David Tenenbaum

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