A groundbreaking study has revealed the solubility of 5-fluorouracil (5-Fu), a key anticancer drug, when dissolved in supercritical carbon dioxide (Sc-CO2). Researchers aimed to understand how 5-Fu can be more effectively delivered via this green solvent, promoting advanced drug formulation.
Conducted by Gholamhossein Sodeifian and his team, the research was published on May 24, 2025, after extensive testing carried out at various laboratories, including the Cedal Pharmaceutical Company based in Iran. With funding from the Iran National Science Foundation, this work stands as the first comprehensive measurement of 5-Fu's solubility under various precise conditions.
The study is significant because 5-Fu is broadly utilized for treating colorectal, breast, head, neck, and certain skin cancers. By analyzing its solubility, scientists can optimize how this drug is formulated and delivered to patients. "Understanding the physicochemical properties of 5-Fu, including its solubility, is key to enhancing drug delivery capabilities," Sodeifian noted.
To obtain the solubility data, the researchers employed UV-vis spectrophotometry, measuring solubility across different pressures (ranging from 120 to 270 bar) and temperatures (from 308 to 338 K). Their findings displayed mole fractions of 5-Fu varying between 2.14 × 10−6 to 7.6 × 10−6, translating to solubility levels between 0.0024 and 0.0176 g/L.
This study introduces machine learning techniques as innovative methods to model the solubility results. Among the models utilized, the Sodeifian model emerged as the most effective, showcasing the lowest absolute average relative deviation (AARD) of 4.12%. "The semi-empirical model suggested by Sodeifian et al. demonstrated superiority with the lowest AARD% (AARD = 4.12%)," the authors remarked.
Notably, the results indicated solubility increases as both pressure and density of Sc-CO2 rise under all studied temperatures. This trend highlights the importance of precise control over experimental conditions when aiming to maximize drug solubility.
Not only did this study contribute valuable solubility data on 5-Fu, it also evaluated various machine learning models. The Decision Tree and Gradient Boosting models performed exceptionally, capturing complex non-linear relationships within the dataset, allowing them to accurately predict solubility trends. "The Decision Tree and Gradient Boosting models’ exceptional performance can be attributed to their capacity to accurately predict solubility of 5-Fu," the authors stated.
The research findings could pave the way for developing Sc-CO2 technology to create micronized and nanosized pharmaceutical particles, significantly impacting drug delivery systems. By enhancing our grasp of how drugs like 5-Fu interact with supercritical solvents, scientists can potentially revolutionize treatment methodologies, promoting more effective and targeted cancer therapies.
With this novel research, the pharmaceutical sector gains not just insights but practical methodologies for improving drug formulation processes. Future investigations are expected to build on these findings, exploring how other drugs may benefit from similar solubilization techniques using supercritical fluids.