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 new amido phosphonate derivative of carboxymethylcellulose with an osteogenic activity and which is capable of interacting with any Ti surface.

A new phosphonate derivative of carboxymethylcellulose (CMC) was recently synthesized (CMCAPh). The phosphonate polysaccharide was obtained by using a carbodiimide-like activating agent for carboxylic groups and 2-aminoethyl-phosphonic acid to create an amide bond between the amine of the phosphonate agent and the carboxylic acids of CMC. The polymer was characterized by (31)P NMR, FT-IR, and potentiometric titration. CMCAPh showed different properties from CMC and its amidated derivative polymer CMCA. The behavior in solution of CMCAPh polymer towards normal human osteoblasts (NHOst) was studied in vitro, monitoring the cell proliferation, cell differentiation, and osteogenic activity and was then compared with the amidic derivative of carboxymethylcellulose (CMCA). Furthermore, CMCAPh was used to coat titania disks with the aim of increasing the osteogenic activity of implant surfaces. The polymer film on the titania surface was characterized by AFM and TOF-SIMS analysis. An ATR FT-IR study was carried out to evaluate the polymer bonding mode onto the titanium surface. Osteoblast morphology was evaluated by SEM. Adhesion analysis of NHOst demonstrated a better adhesion on the titanium surface coated with CMCAPh than on the bare titanium surface.

A thixotropic hydrogel from chemically cross-linked guar gum: synthesis, characterization and rheological behaviour.

Polysaccharide guar gum (GG) was cross-linked in an alkaline solution with polyethylene glycol diglycidyl ether (PEGDGE) to create a new hydrogel. The GG hydrogel was examined by FT-IR spectroscopy, AFM analysis and SEM analysis. The water uptake of the GG hydrogel was measured at different pHs, and rheological studies were performed to verify the thixotropic nature of the material. Rheological studies revealed the pseudoplastic behaviour of the GG hydrogel and its thixotropic nature. AFM analysis on a sample which was subjected to shear stress showed the presence of nanoparticles in the hydrogel. When the sample was left to settle, the gel surface returned to its original homogenous morphology. The thixotropic and injectable nature of the GG hydrogel suggest its possible use in biomedical applications.