The quest for down scale representativeness: how to exploit CFD to design a shear study for vaccines.

In this work, we exploit computational fluid dynamics (CFD) to evaluate stirred tank reactor (STR) process engineer parameters (PEP) and design a scale-down system (SDS) to be representative of the formulation and filling process steps for an Aluminum adjuvanted vaccine drug product (DP). To study the shear history in the SDS we used the concept of number of passages, combined with an appropriate stirring speed down scale strategy comprising of either (i) tip speed equivalence, widely used as a scale-up criterion for a shear-sensitive product, or (ii) rotating shear, a shear metric introduced by Metz and Otto in 1957 but never used as scaling criterion. The outcome of the CFD simulations shows that the tip equivalence generates a worst-case SDS in terms of shear, whereas the rotating shear scaling approach could be used to design a more representative SDS. We monitored the trend over time for "In Vitro Relative Potency" as DP Critical Quality Attribute for both scaling approaches, which highlighted the crucial role of choosing the appropriate scaling-down approach to be representative of the manufacturing scale during process characterization studies.

A smoothed particle hydrodynamics study of the collapse for a cylindrical cavity.

In this study, we propose a mesh-free (particle-based) Smoothed Particle Hydrodynamics model for simulating a Rayleigh collapse. Both empty and gas cavities are investigates and the role of heat diffusion is also accounted for. The system behaves very differently according to the ratio between the characteristic time of collapse and the characteristic time of thermal diffusion. This study identifies five different possible behaviours that range from isothermal to adiabatic.

Gene delivery in the cornea: in vitro & ex vivo evaluation of solid lipid nanoparticle-based vectors.

AIM: Inflammation is a process that underlies sight-threatening ocular surface diseases, and gene supplementation with the plasmid that encodes for p-IL10 will allow the sustained de novo synthesis of the cytokine to occur in corneal cells, and provide a long-term anti-inflammatory effect. This work describes the development of solid lipid nanoparticle systems for the delivery of p-IL10 to transfect the cornea. RESULTS: In vitro, vectors showed suitable features as nonviral vectors (size, Î¶-potential, DNA binding, protection and release), and they were able to enter and transfect human corneal epithelial cells. Ex vivo, the vectors were found to transfect the epithelium, the stroma and the endothelium in rabbit corneal explants. Distribution of gene expression within the cell layers of the cornea depended on the composition of the four vectors evaluated. CONCLUSION: Solid lipid nanoparticle-based vectors are promising gene delivery systems for corneal diseases, including inflammation.