Researchers have made groundbreaking advancements in enhancing the solubility of gemcitabine, an important anticancer drug, by utilizing supercritical carbon dioxide (SC-CO2) as a green solvent. This study aimed to measure the solubility of gemcitabine at various temperatures and pressures and evaluate thermodynamic models to predict its behavior.
Gemcitabine is widely recognized for its efficacy against several cancers, including breast, bladder, pancreatic, and ovarian. Despite its pharmacological importance, gemcitabine suffers from limited solubility, which restricts its bioavailability and therapeutic effectiveness. To tackle this issue, researchers turned to SC-CO2, known for its favorable properties as a solvent.
Dr. G. Sodeifian and colleagues from the University of Kashan conducted detailed experiments measuring gemcitabine solubility within SC-CO2 at temperatures ranging from 308 K to 338 K and pressures between 120 and 270 bar. Their findings show solubility values spanning from 0.1274 × 10−5 to 1.8128 × 10−5 mole fraction, equaling 0.00295 to 0.08489 kg/L.
Remarkably, the study achieved high precision, with standard uncertainties under 5% for the experimental measurements. Results indicated increasing solubility with higher pressures, manifesting more significantly at elevated pressures above 190 to 200 bar. Researchers noted retrograde behavior at this crossover point, where SC-CO2 density influences solute vapor pressure and, hence, solubility.
Utilizing ultraviolet-visible (UV-Vis) absorbance analysis, the research employed two well-established models—Peng-Robinson (PR) and Soave-Redlich-Kwong (SRK)—to predict the solubility of gemcitabine. The PR model performed optimally at 308 K, achieving an average absolute relative deviation (AARD) of 12.58%. Conversely, at higher temperatures, the SRK model excelled, with AARDs varying from 12.93% to 15.68%.
Gemcitabine's solubility prediction also entailed the use of density-based models, whereby the Bian et al. model demonstrated superior accuracy among the six models assessed, with AARDs averaging around 16.62%. This highlights the model’s robustness for pharmaceutical applications.
SC-CO2 has received attention for its eco-friendliness and efficiency. Thanks to its low toxicity, high diffusivity, and ability to penetrate porous materials, SC-CO2 offers significant advantages for drug formulation and manufacturing. Yet, the requirement for elevated pressures entails higher operational costs, typically applying to high-value pharmaceuticals.
The significance of this research lies not only in enhancing gemcitabine's solubility but also paving the way for more efficient drug delivery systems. The potential for SC-CO2 to deliver poorly soluble drugs could revolutionize how pharmaceuticals combat cancer, advancing both treatment efficacy and patient safety.
Future directions of this research may involve exploring the integration of innovative delivery methods utilizing SC-CO2 across other pharmaceutical compounds. Through optimizing solubility and bioavailability, researchers can develop novel platforms for drug delivery systems, elevatively improving therapeutic effectiveness for cancer treatments and beyond.
Overall, this work stands as a substantial step toward realizing environmentally benign and patient-friendly approaches to cancer therapy, setting the foundation for future advancements leveraging SC-CO2 technology.