(631p) Formation and Characterization of PLA/PCL Particles by Supercritical Fluid Technology for Release of Active Agents

Polycaprolactone or simply PCL stands out among the polymers that have been used in the constitution of biomaterials. When compared to other compounds of the same category, it has the appropriate profile as a carrier of drugs that need to be released for long periods. Its biodegradability can be controlled by associating this material with other synthetic polymers such as poly lactic acid, or PLA. The polymer blends formed by the combination of these materials may show improvement in mechanical properties and also on active agents permeability in drug delivery systems. The formation of particles through the use of supercritical fluid technology has been evaluated over the last years, however there has been a major difficulty in the formation of polymeric particulate systems when using only PCL. This fact can be attributed to PCL tendency of forming fibers and films under supercritical conditions. A promising alternative is the association of PCL with PLA, since the use of PLA can successfully result in microparticles formation in supercritical conditions. In this work, the influence of different concentration ratios of PCL and PLA (ranging from 1:9 to 1:1 in polymer solutions at 1% w/v in dichloromethane) was studied on particle formation under controlled conditions of pressure (8 MPa), polymer solution flow rate (0.5 mL/min), CO₂ flow rate (18 g/mL.h) and temperature (40 °C), through the technique of polymer precipitation by SAS, or Supercritical Anti-Solvent method. PCL/PLA particles were successfully obtained particles using this approach. Residual solvent (accessed by head space gas chromatography) was lower than 600 ppm. The mean particle size increased (from 15 to 54 um) increasing PCL concentration from 10 to 50%. It was also noticed that the low miscibility between PLA and PCL, as confirmed by differential scanning calorimetry (DSC), resulted in the formation of aggregated particles. The degree of crystallinity evaluated by X-ray diffraction showed that as the PCL concentration increased in the polymer solution, a reduction of PLA crystallinity was observed. Samples prepared in all tested conditions showed low zeta potential values, regardless of the variation in the PLA/PCL proportion. Samples prepared at low PCL to PLA ratios seemed, then, more appropriated to be used in pharmaceutical applications.