Precision Pills

People who take pills for chronic diseases face schedules that would give an air-traffic controller pause: one kind of medication three times daily with meals, for instance, a second mid-morning and mid-afternoon, and a third at bedtime, as well as several others at various hours.

Michael Cima, a professor in MIT’s department of materials science and engineering, has found a way to use computerized printing technology to simplify the lives of people who must follow these regimens. He and Emanuel Sachs, a professor in the department of mechanical engineering, have created a process that impresses layer upon layer of materials to yield three-dimensional objects with intricate internal structures. Cima believes the technology could make it possible to develop single pills that deliver a variety of specific doses of medicine at planned intervals. The pharmaceutical company Therics, of Princeton, N.J., has secured the exclusive license to commercialize “3-D drug printing” and is sponsoring Cima’s research on it.

Pills are composed of drugs and “excipients”-binders and powders that control the release of medication in the digestive system. The usual procedure is to compress a simple mixture of these ingredients into tablet form. By contrast, the approach chosen by Therics calls for 30 to 50 layers of excipients; within such a matrix, precise amounts of medication would be deposited in key locations. That way “we can control which portion of a tablet dissolves where,” Cima says. One dose deposited in a tablet’s outer layer might be unleashed after, say, an hour, while a dose buried deeper might come into play later.

According to C. William Rowe, an MIT visiting scientist from Therics, a wide range of pill-popping regimens could become less burdensome. Cancer patients could take one pill for both chemotherapy and the ensuing nausea. The technology could also help patients with conditions such as high blood pressure, for which required levels of medication change over the day. “The pressure peaks when these people get out of bed in the morning, so ideally you would like to deliver a high level of medication at exactly that time, and our technology could do this,” Rowe says.

Another benefit could be improved dosage control. With traditional pharmaceuticals manufacturing, a drug may not always be evenly distributed among excipients; different pills can wind up with somewhat different doses. But in the new process, the drop-on-demand nozzle used to deposit medication would assure accurate doses in every tablet, Cima notes.

And 3-D drug printing might help companies bring more drugs to market. The reason, Cima says, is that the technology would permit them to take better advantage of “combinatorial chemistry,” a means of rapidly testing the efficacy of molecules for a particular use. Combinatorial chemistry has doubled the number of possible therapeutic agents in R&D pipelines. But finding appropriate molecules is only the first step in drug development. Researchers must combine them in the right way with the right excipients-and therein lies a problem.

Firms must run trials on several subtly different combinations of drug and excipients. The use of conventional technology, which is designed to produce a large volume of pills at one time, requires making many more than are needed. for each trial. Since the number of new drugs in the pipeline has been doubled, the cost of conventional pill-making methods for drug trials could be prohibitive. But the new, threedimensional method could allow researchers to produce small batches of pills with different formulations, sharply reducing waste.

Although various technical challenges still must be overcome, Cima says Therics is poised to start the first stage of tests for commercial production, so that “pills made this way might be available as soon as a year from now.” Therics’s Rowe is more guarded, stressing that the U.S. Food and Drug Administration (FDA) has yet to approve the process. But the difference between receiving approval for a manufacturing process, as opposed to getting it for an actual drug, is significant, Cima remarks. “It’s sort of like going to the FDA and saying, ‘we have a new pill press here.’ The list of issues they want to look at is fairly short.”