Dextran or Hydroxyethyl Starch in Sprayfreeze-Dried Trehalose/Mannitol Microparticles Intended as Ballistic Particulate Carriers for Proteins

The goal of this study was to clarify the effects of dextran 10 kDa on the properties of spray‐freeze‐dried microparticles for use with ballistic injectors. A novel carrier of trehalose, mannitol, and the polymer is known to maximize particle density. Measurements of T′g showed that the dextran anti‐plasticizes the trehalose/mannitol, but also undergoes phase separation. The product temperature exceeded T′g during primary drying. The collapsed particles can therefore be explained by plastic flow of the freeze concentrate. DSC of the powder showed Tg at 45°C and, in the first scan, a wide endothermic melting peak caused by mannitol recrystallization. Catalase showed 35% activity loss on rehydration of its spray freeze‐drying (SFD) powder, which was improved in the TM/D (3:3:4) formulation, but not up to that level seen with either trehalose or mannitol alone. The dextran 10 kDa, which is vital to maximize particle density, was therefore detrimental to protein integrity during SFD, as also found with a 65-72 kDa dextran. Hydroxyethyl starch (HES) 200 kDa gave similar, limited stabilizing effects on the protein. The proportion of polymer in the formulation should be low to minimize protein damage, whilst high enough to give required particle morphology and density. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2296-2309, 2007