Quality-by-Design Approach to Process Intensification of Bioinspired Silica Synthesis
Quality-by-Design Approach to Process Intensification of Bioinspired Silica Synthesis
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DOI：
10.1021/acssuschemeng.3c07624
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发表时间：
2024-03-08
影响因子：
8.4
通讯作者：
Patwardhan，Siddharth V.
中科院分区：
文献类型：
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作者：
Manning，Joseph R. H.;Brambila，Carlos;Patwardhan，Siddharth V.
由于其大分子性质，表征纳米材料具有挑战性，需要一套物理化学分析来完全解析其结构。因此，它们的合成和放大是众所周知的复杂，特别是当与小分子或块状晶体材料相比时，其可以单独从核磁共振（NMR）或X射线衍射（XRD）提供独特的指纹。在这项研究中，我们通过采用三步质量设计（QbD）方法来扩大生物启发二氧化硅纳米材料的规模来应对这一挑战，展示了其对这类材料合成规模扩大和强化的实用性。首先，我们确定了材料比表面积，孔径分布和反应产率作为关键质量属性（CQA），可以通过改变反应条件进行精确测量和控制。然后，我们确定了控制生物启发合成特性的关键工艺参数（CPP），探索了不同的工艺路线，加入了商业试剂，并优化了试剂比例，将二氧化硅特性与原始CQA值进行了比较，以确定每种CPP的可接受限度。最后，我们通过增加试剂浓度来强化合成，同时结合优化的CPP，从而修改生物启发二氧化硅合成，使其与现有的制造方法兼容。我们从ca. 1.1添加剂浓度从38 g/L降低到38 g/L左右。1 ~ 0.04g/g产品，大大降低了合成成本和废物产生。这些结果表明，需要绘制关键工艺参数对材料形成途径和CQA的影响，以加速从实验室到市场的规模扩大和过渡。
Characterizing nanomaterials is challenging due to their macromolecular nature, requiring suites of physicochemical analysis to fully resolve their structure. As such, their synthesis and scale-up are notoriously complex, especially when compared to small molecules or bulk crystalline materials, which can be provided a unique fingerprint from nuclear magnetic resonance (NMR) or X-ray diffraction (XRD) alone. In this study, we address this challenge by adopting a three-step quality-by-design (QbD) approach to the scale-up of bioinspired silica nanomaterials, demonstrating its utility toward synthesis scale-up and intensification for this class of materials in general. First, we identified material-specific surface area, pore-size distribution, and reaction yield as critical quality attributes (CQAs) that could be precisely measured and controlled by changing reaction conditions. We then identified the critical process parameters (CPPs) controlling bioinspired synthesis properties, exploring different process routes, incorporating commercial reagents, and optimizing reagent ratios, comparing silica properties against original CQA values to identify acceptable limits to each CPP. Finally, we intensified the synthesis by increasing reagent concentration while simultaneously incorporating the optimized CPPs, thereby modifying the bioinspired silica synthesis to make it compatible with existing manufacturing methods. We increased the specific yield from ca. 1.1 to 38 g/L and reduced the additive intensity from ca. 1 to 0.04 g/g product, greatly reducing both synthesis cost and waste production. These results identify a need for mapping the effects of critical process parameters on material formation pathways and CQAs to enable accelerated scale-up and transition from the lab to the market.