(189b) A Quality-By-Design Approach to Process Intensification of Green Nanomaterials

Nanomaterials “specification” include a broad array of physicochemical features, especially if they are non- or semi-crystalline, contrasting with small molecules or bulk crystalline materials which can be provided a unique fingerprint from NMR or XRD alone. As such, their synthesis and scaleup is notoriously complex and their complex. In this study, we therefore apply the Quality by Design (QbD) paradigm during noncrystalline nanomaterial process intensification, demonstrating both its applicability to this class of materials and its importance in scaling up manufacturing.

The presentation, using bioinspired silica, will show results on how process decisions, feedstock concentration, and additive concentration affect product quality. We analysed various material properties to study the variations caused by deliberate changes to the synthesis methodology. We found that primary particle size and mass fractal dimension measured by USAXS was unable to distinguish different synthesis routes; conversely particle size distribution measured by TEM were incomparable between different synthesis methods, preventing meaningful analysis. In contrast, silica speciation and bulk textural properties (i.e. BET surface area and pore size distribution) were more sensitive to minor changes in the synthesis conditions than inter-batch variation. This helped us define the yield and bulk porosity as the critical quality attributes (CQAs), which were sensitive to synthesis conditions.

We then defined several critical process parameters (CPPs) to the synthesis at scale and assessed their impact on the CQAs. Switching to industrial feedstock from research-grade precursor led to the introduction of broad mesopores in the resultant materials. Once these modifications had been incorporated, we intensified the synthesis (increased yield per volume) by increasing the precursor concentration (and reducing additive concentrations). Interestingly, increasing the initial precursor concentration to similar levels as current industrial processes provided yields of ca. 98 %mol. Overall, we successfully applied all the changes to synthesis to make it compatible with existing industrial silica manufacturing. We increased the specific yield from ca. 1.1 g/L to ca. 38 g/L, and reduced the additive intensity from ca. 1 g/g product to 0.04 g/g, representing a significant reduction in synthesis cost and waste production. During the process intensification, it was observed that the synthesis was prone to gelation rather than coagulation under certain conditions. These results have identified a need for mapping the effects of CPPs (including scale-up) on the formation pathways and the CQAs. Such understanding can also enable process flexibility where materials of different grades can be produced using the same platform, with minor variations to the CPPs.