Formulation of 5-fluorouracil by the Atomized Rapid Injection Solvent Extraction (arise) Process

The use of dense gases (DGs), particularly CO2, as solvents for pharmaceutical reformulation has attracted great attention due to the excellent tunability of their solvating power. Other attractive advantages for processing of active pharmaceutical ingredients include mild processing temperatures and limited usage of organic solvents. In this work, we applied a novel process based on the DG technology, the Atomized Rapid Injection Solvent Extraction, for encapsulation of 5-fluorouracil (5FU), a popular chemotherapeutic agent, with poly-L-lactic acid (PLLA). The initial polymer to drug ratio (RPLLA:5FU), temperature and pressure were selected for the study. The effect of these conditions on particle size distribution, drug loading, encapsulation efficiency and drug recovery of products were investigated by using a full factorial design (2). The results showed that, within the experimental conditions, none of the tested variables had a statistically significant effects on particle size distribution and total drug recovery. Drug recovery percentages for the experiments were all greater than 79%. Temperature and RPLLA:5FU had significant effect on drug loading and encapsulation efficiency, while pressure had no effect. Generally, operation at low temperature and low RPLLA-5FU was preferable for the production of PLLA-5FU composites with high drug loading and encapsulation efficiency. The highest encapsulation efficiency (24%) was associated with the highest drug loading (7%), and was achieved at 25°C, 110 bar and RPLLA:5FU = 3. Drug loadings were higher at 25°C than at 35°C. They were higher than those processed by the Solution Enhanced Dispersion by Supercritical Fluids and comparable to the spray drying method.