NSAID Drugs Release from Injectable Microspheres Produced by Supercritical Fluid Emulsion Extraction

Supercritical fluid emulsion extraction is an innovative technology that uses supercritical carbon dioxide (SC‐CO2) to extract the dispersed oily phase of an emulsion. This technology was used to produce poly‐lactic‐co‐glycolic acid (PLGA) microspheres charged with two common NSAIDs: piroxicam (PX) and diclophenac sodium (DF). Single (O/W) and double (W/O/W) emulsions were tested and a comparative study between the characteristics of the microspheres obtained by SC‐CO2 extraction and the ones produced by conventional solvent evaporation (SE) is proposed. Varying the droplet dimensions, microspheres with mean diameters (MDs) of 1, 2, and 3 µm were obtained; however, the microspheres produced by SC‐CO2 gave always a better reproduction of the MD of original droplets because aggregation phenomena often modify the mean size and distribution of the microparticles produced by SE. Moreover, very efficient drug loadings (88% w/w of DF in PLGA using W/O/W emulsion and 97% of PX w/w in PLGA starting from O/W emulsion) were measured in the products obtained by SC‐CO2, respectively; whereas, the SE produced a drug loading of 30% in the case of double emulsion and of 70% for single emulsion. Solvent residue of 10 ppm was also measured by SC‐CO2 technology against the 600 ppm of the SE products. The release profiles of the entrapped drugs were also monitored to check the structure of the microspheres produced by this new technology. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1484-1499, 2010