NSAID Drugs Release from Injectable Microspheres Produced by Supercritical Fluid Emulsion Extraction  G. Della Porta, N. Falco, E. Reverchon  Journal of Pharmaceutical Sciences  Volume 99, Issue 3, Pages 1484-1499 (March 2010) DOI: 10.1002/jps.21920 Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 1 Schematic representation of the apparatus. V, high pressure vessel; O, oven; DP, diaphragm pump; CB, cooling bath; CCO2, CO2 cylinder; MV, micrometering valve; OV, on‐off valve; BP, back‐pressure valve; M, manometer; TC, termocouple; SC, heat exchanger; R, rotameter; DM, dry test meter; LS, liquid separator; CV, collecting vessel. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 2 Cumulative size distribution curves describing the droplets in single (a) and double (b) emulsions obtained fixing all other parameters and varying PLGA concentration in the oily phase. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 3 (a and b) Examples of Optical Microscope (MO) images of the emulsions produced. (a) O/W emulsion: 20:80. Oil phase with PLGA 5% w/w and PX 10% w/w of PLGA; (b) W/O/W emulsion: 2:18:80. Oil phase with PLGA 7.5% w/w and DF 10% w/w of PLGA. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 4 SEM image of PLGA/PX microspheres (MS 1.06 µm; SD 0.43 µm) prepared by SC‐CO2 extraction of an emulsion (2.5% w/w of PLGA in the oily phase; PX charged is 10% w/w of the polymer). Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 5 (a and b) AFM images of PLGA microspheres obtained by SC (a) and by SE (b) starting from the same O/W emulsion (20:80) with an oil phase formed by EA containing 7.5% w/w of PLGA (PX is 10% w/w of PLGA). Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 6 SEM images of PLGA/DF microspheres produced by SC (left side) and by SE (right side) varying PLGA amount in the oily phase of the emulsion from 2.5% w/w (a), 5% w/w (b), and 7.5% w/w (c), respectively (DF is 10% w/w of PLGA). White arrows highlighted the formation of DF crystals during the SE process. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 7 EDX images of DF/PLGA microspheres (PLGA amount in the oily phase 7.5% and charged with 10% w/w of DF). The chlorine atom signal is used to recognize the presence of DF uniformly spread on the microspheres surface. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 8 Comparison of X‐ray patterns of untreated PX and PLGA compared with PLGA/PX microspheres obtained by SC and SE technology. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 9 Comparison of X‐ray patterns of untreated DF and PLGA compared with PLGA/DF microspheres obtained by SC and SE technology. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 10 Comparison between the PX release profiles from PLGA microspheres with the same mean diameter (MD 2 µm; SD 0.8 µm) and charged with different theoretical drug loadings of 5 and 10% w/w, respectively. The release profiles of pure PX are also proposed, for comparison. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 11 SEM images of PLGA eroded microspheres after about 6 days of PX release. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 12 Comparison between the release profiles of PX from PLGA microspheres with different mean diameters (MD) and charged with the same theoretical drug loading of 10% w/w. The release profiles of pure PX are also proposed, for comparison. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions

Figure 13 Comparison between the release profiles of DF from PLGA microspheres with different mean diameters (MD) and charged with the same drug theoretical loading of 10% w/w. The release profiles of pure DF are also proposed, for comparison. Journal of Pharmaceutical Sciences 2010 99, 1484-1499DOI: (10.1002/jps.21920) Copyright © 2010 Wiley-Liss, Inc. Terms and Conditions