Regulating particle morphology during a spray freeze drying ...

INTRODUCTION TO SPRAY FREEZE‐DRYING 7larger than 75 μm, small unaesthetic bruises are possible; even larger particles couldcause significant skin damage. If the mean mass aerodynamic diameter is less thanabout 20 μm, the vaccines can be stopped or deflected by the skin surface and do notpenetrate into the skin [Burkoth et al. 1999]. The injection velocities can differ from 200– 3,000 m/s, whereas ideal particle densities for EPI lie between 100 – 25,000 kg/m 3 ;ρ P values between 800 and 1,500 kg/m 3 have been suggested as optimal [Sarphie andBurkoth 1997].Physical and mechanical requirementsuniform size (∼30 – 50 μm in diameter)uniform (spherical) shapehigh density (800 – 1500 kg/m 3 )sufficient mechanical strength to withstandimpact with the skinPharmaceutical and biologicalrequirementsappropriate parenterally acceptableexcipientsshort / long term chemical and physicalstabilityappropriate biological properties oncedelivered to the skinviable manufacturabilityTable 1. Powder requirements for needle‐free powder injection according to[Ziegler 2006].Vaccine powders must achieve sufficient mechanical durability to sustain the enormousphysical stress during EPI. Firstly, the particles are entrained by the helium gas whenthey are rapidly accelerated to several 100 m/s. Secondly the strong impact on theepidermis surface forces the particles to decelerate rapidly [Prestrelski et al. 2002].Ziegler et al. [Ziegler et al. 2006] demonstrated that some carbohydrate co‐solutes donot only stabilize proteins during the powder manufacturing process, but also protectthe API from vaccination‐induced stress. Based on the results from catalase SFDparticles, the protein was more damaged by mechanical stress (shear and impact) thanby static pressure. Pure catalase particles reacted more sensitive to any kind of stressthan those formulated with carbohydrates.