Transforming Oral Cancer Therapies: Enhanced Bioavailability and Reduced Variability with Innovative Drug Formulations

Cancer treatments have seen some pretty incredible breakthroughs over the years, especially with the introduction of targeted therapies like tyrosine kinase inhibitors (TKIs) such as dasatinib and sorafenib. They offered better treatment outcome with much less side effects compared to chemotherapy. But, as amazing as they are, there is still a pretty big limitation: getting these drugs to work well when taken orally. It’s not as simple as swallowing a pill and expecting it to work perfectly. These drugs can be unpredictable, and that’s been a real problem for both patients and doctors. The issue boils down to how these medications interact with the body. TKIs are notoriously tricky because they don’t dissolve easily in general and some only when the environment is very acidic—like your stomach. If someone’s stomach acid levels aren’t quite right, which can happen naturally or because they are taking medications like antacids or proton pump inhibitors, the drug might not dissolve properly. That means less of the medicine gets absorbed, and its effectiveness can take a hit. What’s worse, the amount of the drug that ends up in the bloodstream can vary wildly, not just between different people but even for the same person on different days. This is where things get even more frustrating. Because of these challenges, patients are often stuck following strict instructions about when and how to take their medications—on an empty stomach, with water only, and definitely not alongside certain foods or medications. To this account, Per Andersson, Magnus Brisander, Charlotta Liljebris, and Gérald Jesson at Xspray Pharma, in collaboration with Professor Hans Lennernäs from the Department of Pharmaceutical Biosciences at Uppsala University, demonstrate that Xspray’s innovative HyNap technology produces stable amorphous solid dispersions (ASDs) of protein kinase inhibitors (PKIs) that are easily dissolved and have pH-independent absorption, resulting in more consistent drug uptake even when taken with food or pH-increasing medications. The hope is that this new approach will take out a lot of the guesswork of using these medications. If the drug dissolves well no matter what, patients wouldn’t have to worry about sticking to strict dosing rules or avoiding certain foods and medicines. They could just take their pills and focus on getting better. For doctors, it means more consistent drug levels in the bloodstream, making it easier to fine-tune treatment. The new research paper is now published in Journal Clinical Pharmacology in Drug Development.

The first part of their work focused on dasatinib, a drug that’s notoriously hard to absorb because it doesn’t dissolve well unless it’s in a very acidic environment. They created a new version called XS004, where the drug was blended into a polymer to keep it in a supersaturated state after being swallowed. Then they tested it on healthy volunteers in a clinical study, comparing it to the traditional crystalline version of dasatinib. The results were exciting: XS004 achieved the same therapeutic concentration levels as the original drug but at a 30% lower dose. That’s a big deal because it reduces the drug burden on patients. Even better, the new formulation was far more predictable. The variation in how the drug performed between different people—or even in the same person on different days—was cut down by up to four times. This kind of consistency could make a real difference in how reliably the drug treats cancer.

They didn’t stop there. The team also worked on improving sorafenib, another tricky drug with similar issues. They developed a new ASD formulation called XS005, which they tested in a similar way. This version increased how much of the drug was absorbed by 45% compared to the original crystalline version, and it also significantly reduced the ups and downs in drug levels in the bloodstream. While XS005 didn’t reach full bioequivalence at the dose they tested, it still showed massive potential as a more effective option. It was clear the new formulation was a step in the right direction, even if it might need a little more tweaking. To figure out why these new formulations worked so well, the researchers ran lab experiments to measure how the drugs dissolved under various conditions. The results were remarkable. For dasatinib, the ASD formulation was at least ten times more soluble in less acidic environments than the traditional version. Sorafenib was even more impressive, with solubility increasing by up to 800 times in some cases. These improvements explained why the drugs performed so much better in the clinical studies—they were simply dissolving and absorbing more efficiently. This research matters because it’s not just about making these two drugs better. It’s about changing the game for other medicines that face the same kinds of problems. By addressing the basic issue of how drugs dissolve and absorb, this technology could pave the way for more reliable, easier-to-use treatments for cancer and other diseases. At the end of the day, it’s about giving patients more consistent, effective therapies without adding extra stress to their lives. And that’s something everyone can appreciate. But the implications of Professor Hans Lennernäs and colleagues study go way beyond dasatinib and sorafenib. What the researchers have done is create a platform that could be used for all kinds of drugs with similar issues. Many medications struggle with poor solubility and inconsistent absorption, especially those that are sensitive to the stomach’s pH levels. This technology could change that, making it possible to develop better versions of these drugs. For instance, future research in other TKIs that could benefit from ASD technology include  product  candidates nilotinib, axitinib and cabozantinib. These drugs could benefit from improved solubility, minimized impact of pH variations, enhanced pharmacokinetics, and potentially reduced dosages for patients.