Supercritical Anti-solvent Precipitation of Sodium Ibuprofen

In recent years, significant effort has been devoted to the development of drug formulation with the purpose of targeting and controlled release. The micro/nanosizing of drugs has been identified as a potentially effective and broadly applicable approach. In the pharmaceutical industry several conventional techniques have been utilized for particle size reduction. The disadvantages of these techniques are thermal and chemical product degradation, high energy requirements, use of large amounts of solvent and broad particle size distributions. Therefore, the search for more effective techniques applicable to drugs formulation continues. Accordingly, the objective of this work was to apply the Supercritical Anti-Solvent (SAS) process to nanosize sodium ibuprofen, a nonsteroidal anti-inflammatory drug, evaluating the effect of operational parameters in particle size and morphology. Initially the solute (sodium ibuprofen) was dissolved in acetone and then the operational parameters for SAS process were regulated. The anti-solvent, supercritical CO2 (SC-CO2) which presents high diffusivity, was introduced into the precipitation chamber, in a concentric tube together with the acetone/ibuprofen liquid solution. The complete miscibility between acetone and SC-CO2 causes the ibuprofen precipitation. The following ranges evaluated the SAS process: pressure (80-140bar), temperature (35-55C), solute concentration (0.5-1.5mg/mL) and solution flow rate (1-3mL/min). The process used 99.9% pure CO2, applied at constant flow rate of 1kg/h. The particles obtained from all conditions were evaluated by their size and morphology, using a scanning electronic microscopy, and their thermal profiles by differential scanning calorimetry. All conditions applied reduced the particle size from 144±87μm to 87-380nm.