Drugs work best when our digestive system can absorb them completely so they can pass into the bloodstream and become available where they are of most use. Because most drugs are only partly soluble in the watery environments inside our bodies, new drug products are increasingly using oil-based ‘soft-gel’ formulations that keep the active ingredient in a dissolved form. Studies of how oily (lipid-based) drug products behave in our digestive system are helping to guide the development of more effective drug products.

Dr Ben Boyd and his colleagues at the Monash Institute of Pharmaceutical Sciences (MIPS) are using an ‘artificial tummy’ (aka an ‘in vitro digestion model’) and other methods to examine what happens when lipid-based drug products undergo digestion in the human gut.

“When lipids and fats are digested, they form particles and other structures with nanometre-scale dimensions,” Ben says. “Our aim is to learn which structures provide the right environment for maximum drug absorption and to find ways to manipulate these structures by ‘tuning’ the lipids.”

The pharmaceutical industry is taking a keen interest in this area because an estimated 25 to 40 percent of drug candidates fail to lead to successful drug products due to solubility limitations.

Ben and his colleagues Dallas Warren and Mette Anby recently set up their artificial tummy at the Australian Synchrotron, where they used the small angle x-ray scattering (SAXS) beamline to follow what happens when lipids are exposed to conditions similar to those found in the human gut.

“Our initial synchrotron findings show that unstructured lipid systems definitely form nano-scale structures during digestion, including lamellar, inverse hexagonal and cubic phases,” Ben says. “The types, proportions and timing of the structures formed depend largely on the original lipid. We can also detect drug precipitation.”

Ben says this new information about the link between nano-structure and how well drugs remain in a dissolved state will help researchers to reverse-engineer the best formulations for keeping drugs dissolved longer during digestion.

“We believe these promising findings will eventually lead to more rational drug design principles, less reliance on animal studies and more efficient development of products.”

“While we could have conducted these studies at a synchrotron overseas, why would we? The Australian Synchrotron is a state-of-the-art facility with a great team of beamline scientists helping us out, we can dash back to our lab in Parkville at a moment's notice to get materials for an 'off-the-cuff' experiment that might arise from a new result, we don't need to package up and risk damage to our own equipment (in both directions) and the opportunity to crash on your own pillow is highly attractive!”

The next stage for Ben and his colleagues will involve more extensive studies into the evolution of structure with different lipids, using different drug types to get to the heart of the problem. Ben also plans to extend the studies into an in vivo model to see how well the 'artificial tummy' results relate to the in vivo reality.

“That will be quite a challenge,” he says.