Three Pills? I Only Want One!

How they crammed three AIDS drugs into one tablet.

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On Wednesday, the Food and Drug Administration approved a new pill called “Atripla” that combines three anti-retroviral medications used for the treatment of AIDS. Doctors hope that the three-in-one drug will make it easier for patients to keep up with their daily regimen. Is it hard to put different medications in the same pill?

No. Anti-retroviral cocktail pills have been around for some time in the developing world. Indian pharmaceutical companies and the government of Thailand produce these single-dose medications using older versions of the same kinds of drugs that go into Atripla. Even in America, two of the three Atripla drugs already come in a single pill called Truvada.

The process for making a combination can take longer in the United States. The FDA must approve the new drug even if it has already looked at each component. (In this case, FDA approval took only three months under a special program to promote life-saving drugs.) Another factor that might have delayed Atripla is the fact that its three active ingredients—efavirenz, emtricitabine, and tenofovir disoproxil fumarate—are sold commercially by two different companies, Bristol-Myers Squibb and Gilead Sciences. The drug could hit the market only after all the necessary business and legal agreements had been reached. The ATRIPLA trademark belongs to a joint venture known as “Bristol-Myers Squibb & Gilead Sciences, LLC.”

Putting different drugs into the same pill can be as easy as blending them into the same powder. But some ingredients may not mix well—they’ll tend to separate like oil and water—or they could have a reaction when they come into contact with each other. Combining chemicals might lower their melting point, for example. If the melting point of a compound dips too low, your bottle of pills will turn into medicinal soup.

Manufacturers can try to keep different drugs separate inside the same pill. They can coat the powdery particles of one ingredient before mixing it with another, to make sure that they don’t actually touch. They might also try to layer different ingredients within the same pill.

Compounding pharmacies produce single-dose combinations of drugs on a custom basis. One trick they use to keep drugs separate is to put a pill into a large capsule and then fill the rest of the space in the capsule by sprinkling in the powdered form of another drug. (Compounding pharmacies don’t need FDA approval for their concoctions. They’re regulated by the state boards of pharmacy.)

Once a pharmaceutical company has figured out a way to mix ingredients into a single pill, they have to make sure the new combination drug works. They have to test it in clinical trials to make sure that each component is making its way into the bloodstream at an appropriate rate. Since different ingredients may be most effective if taken at certain times of day, the companies also have to figure out the best way to prescribe the combination.

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Explainer thanks Loyd Allen of the International Journal of Pharmaceutical Compounding, Rowena Johnston of the Foundation for AIDS Research, and Joshua Wenderoff of the International Academy of Compounding Pharmacists.