As PLGA/PVA emulsions could be successfully spray dried when spiked with P-407, it was tested whether the addition of PVA and trehalose to a PLGA/P-407 emulsion could positively influence nanoparticle stability. The resulting PDI of 0.35 was only slightly better than when using trehalose and leucine. This indicates that the presence of PVA is already needed during the emulsion step to exert its stabilizing effect during spray drying. An acceptable PDI of 0.23 could only be achieved when spray drying a suspension previously precipitated by solvent displacement after the addition of PVA and trehalose. However, the nanoparticle yield was unacceptable for all tested formulations of PLGA/P-407 particles (Fig. 4) and was considerably lower than previously reported for focused ultrasound followed by solvent displacement (9). The superiority of PVA may be attributed to the formation of a thicker and denser surface layer (indicated by the larger resulting hydrodynamic particle sizes) and stronger surface binding and retention (23,24), whereas P-407 adsorbs weaker with its middle poly(oxypropylene) block (25).
Fig. 4 Resulting nanoparticle yield after spray drying of PLGA/P-407 double emulsions with and without the addition of different matrix excipients. Nanoparticles were isolated from the matrix after reconstitution of the complete batch in purified water, then aggregates were removed by filtration, and the mass was determined after drying. The nanoparticle yield with K30 was too low to determine by weighing and, as such, is reported as 0