A closer look at the unfolded drug-delivery system (left) and capsule containing it (right), shown next to a penny for scale

Daily birth control pills allow women to manage their fertility, but this method of contraception relies on a user remembering to take her pill at the same time every day. A team led by investigators from the Brigham and Massachusetts Institute of Technology (MIT) is designing a new type of capsule that could deliver an oral contraceptive that only needs to be taken once a month, helping improve adherence and reducing the risk of unplanned pregnancy.

Building on previous research to develop slow-release pills that can reside in the stomach for days or weeks, the team reported in Science Translational Medicine that, for the first time, it has achieved month-long delivery in preclinical models.

If safe and successful in humans, the capsule could help remove some of the challenges associated with a daily birth control pill. In a multinational survey, about half of women taking an oral contraceptive reported missing at least one dose over a three-month period. Among women using oral contraceptive pills, the chance of pregnancy is about 9 percent every year.

“Our capsule represents a major advancement toward providing women with a once-a-month contraceptive. For many, this may be hard to believe. But our preclinical data is encouraging us along that road,” said co-corresponding author Giovanni Traverso, MB, BChir, PhD, a gastroenterologist and physician-researcher at the Brigham and MIT. “We began our work on extended-drug release by working with treatments for malaria, tuberculosis and HIV. But early on, we were having conversations about the potential impact that this approach could have for family planning. We wanted to help empower women with respect to fertility control and are pleased to report our progress toward that goal.”

We create breakthroughs. It's in our DNA logo.The team designed a drug-delivery vehicle that consists of six arms joined by an elastic-coated core. The arms were loaded with the oral contraceptive drug levonorgestrel and folded up into a capsule that can be swallowed. Once in the stomach, the arms unfold and have a span that is larger than the opening between the stomach and small intestine. This allows the system to stay in the stomach, where it can release the drug in controlled doses over time. After a month, the unfolded capsule is broken down by the stomach and safely passes through the gastrointestinal tract.

The research team tested the concentration of oral contraceptive over time in a porcine model and measured the presence of the drug in the bloodstream for the extended-release form versus an immediate-release tablet. For the tablet, dosage tapered off after six hours. For the extended-release capsule, the team observed concentrations of the drug for up to 29 days.

Work is now underway to bring the extended-release pill closer to human trials. Next steps will include scaling up manufacturing processes and safety evaluations.