Researchers at Brown University (RI, USA) have developed a magnetic system that can hold a pill in the correct place for optimal
absorption. The technology has been safely tested in rats and could be used as a new treatment. Pharmaceutical Technology
Europe spoke to Edith Mathiowitz, Professor of Medical Science in Brown’s Department of Molecular Pharmacology, Physiology
and Biotechnology, to find out more.
How does the technology work?
Due to inter‑patient and intra‑patient variability in gastrointestinal (GI) transit time, pills do not always dissolve at
the expected location, but our magnetic technology enables a pill to remain in the area of interest for a user‑defined duration.
The magnetic pill is dosed orally, and involves the use of a gelatine capsule containing a tiny magnet and an external magnet
that can precisely sense the force between it and the pill. When the pill reaches the desired region of drug delivery — based
on gastrointestinal transit time and confirmed by fluoroscopy — an external magnet approaches the desired site of retention
until a safe, maximum force is reached, as measured by a load cell. Once this force is reached, the external magnet moves
away from the internal magnet until a minimum force is reached and then the cycle repeats for a user‑defined period of time.
While the external magnet is cycling between force boundaries, the magnetic pill is retained safely and effectively. After
the conclusion of the experiment, the magnetic pill is excreted.
Edith Mathiowitz. Credit: Mike Cohea/Brown University
As long as the pill does not dissolve too quickly, the added residence time in the desired location enables more effective
dissolution. The pills can also be designed to overestimate the amount of time prior to dissolution, making the target far
more achievable and reproducible provided that retention is reliable and safe, which were among our high priority design goals
in creating our new system.
Why did you and the other researchers feel that improvements were needed in the area of gastrointestinal drug adsorption?
The number of approved and pipeline therapeutics exhibiting poor absorption or a narrow absorption window is increasing. We
sought to create a system that would enable investigators to test where their compounds achieve the greatest absorption and
to determine if prolonging retention for any amount of time would enable oral dosing of a therapeutic that would, otherwise,
In particular, there is also a large unmet need of localised delivery for GI pathophysiologies, such as inflammatory bowel
disease and esophageal cancer, which investigators have been working towards for many years. Our safe oral delivery system
would have great therapeutic potential in this area because a number of therapeutics would benefit from prolonged localisation
either at their site of action or their site of greatest absorption.
The system could also be used to investigate the absorption of new drugs in various locations to determine where they are
best absorbed. This information could be extremely useful for designing an optimal drug delivery system for a new compound.
In addition, the system could be beneficial for evaluating existing delivery systems for optimal operation.
Other research has been conducted with magnetic pills. How did you overcome the major challenge of developing a system safe
to use in the body?
Our major safety innovation was to monitor the inter‑magnetic force experienced between the magnetic pill and the external
magnet, and then to cycle between safe force boundaries. The cyclical application of force is meant to alleviate localised
stress periodically, while still maintaining the pill for prolonged durations.
One of the major challenges of the work was defining a safe upper force limit that would still achieve sufficient inter-magnetic
force to retain the magnetic pill, and then to design a feedback system that would cycle between the lower and upper force
limits with a frequency that both minimised tissue damage and maximised retention efficacy. As such, the device and testing
protocol underwent significant iteration on the way to achieving safe and effective magnetic pill retention.
How do you envision the system being used in a commercial world?
The research is still at an early preclinical stage. In a commercial world, we envision the system first being applied to
severe pathophysiologies in which other therapeutic modalities are insufficient; namely cases of severe inflammatory bowel
disease, or GI cancers in an in-patient setting.
Ultimately, if proven safe and effective in a clinical environment, we also envision use in an outpatient setting in which
magnetic tracking rather than fluoroscopy is used to confirm the location of the magnetic pill.
The next challenges will be to incorporate drug into the system and then to transition into large animal studies. We will
prioritise the oral delivery of therapeutics for disease states that currently require more invasive interventions, as well
as therapeutics that otherwise exhibit such low oral absorption that they require alternative routes of administration. We
would also like to work with investigators who are developing new chemical entities to investigate the site specificity of
absorption or potential to increase bioavailability with prolonged retention.