Poozesh Sadegh, Algasem Faisal, Azad Mohammad A, Marsac Patrick J
Mechanical Engineering Department, Tuskegee University, Tuskegee, AL, 36088, USA.
Chemical, Biological and Bioengineering Department, North Carolina A& T State University, Greensboro, NC, 27411, USA.
Pharm Res. 2022 Sep;39(9):2033-2047. doi: 10.1007/s11095-022-03248-4. Epub 2022 Apr 6.
The aim of this work is to present a modeling tool to describe drying kinetics and delineate evolving physical and chemical behavior of multicomponent droplets during drying. Conservation equations coupled with population balance equations (PBE) are used to achieve this goal. Modeling results are gauged with single salt-water droplet drying from literature and show congruent trends. This model is then extended to a more complex system: various droplet sizes containing methanol (solvent), Felodipine (active ingredient), and PVP (polyvinylpyrrolidone as excipient). The FIB-SEM (Focused-Ion Beam Scanning Electron Microscopy) imaging results from spray-dried particles produced with similar formulation and processing conditions are consistent with phase behavior predicted by the model. The results show competing impacts of transport phenomena on the intermittent shell formation process and final particle structure and chemical heterogeneity. Solute diffusion, solvent efflux, and intra-drop flow impact the model system. It is found that shell formation follows a fluctuating profile where the initial precipitation of the dissolved species on the droplet surface is dampened, and nucleated particles become dispersed periodically until the shell becomes strong enough to withstand internal circulations. These internal effects are dependent on droplet size and are pronounced for larger droplets. That is, the particle phase behavior and physical nature are functions of the atomized droplet size. Stemming understating from this study would inform an optimized unit, operating in target design space. This would provide better product quality control and minimize discrepancies observed in process development during the early phase vs. commercial scale.
这项工作的目的是提出一种建模工具，用于描述干燥动力学，并描绘多组分液滴在干燥过程中不断演变的物理和化学行为。通过将守恒方程与种群平衡方程（PBE）相结合来实现这一目标。利用文献中关于单盐水滴干燥的实验结果对建模结果进行了评估，结果显示出一致的趋势。然后，该模型被扩展到一个更复杂的系统：包含甲醇（溶剂）、非洛地平（活性成分）和聚乙烯吡咯烷酮（作为辅料）的各种液滴尺寸。聚焦离子束扫描电子显微镜（FIB-SEM）对在相似配方和加工条件下制备的喷雾干燥颗粒的成像结果与模型预测的相行为一致。结果表明，传输现象对间歇壳层形成过程以及最终颗粒结构和化学不均匀性具有相互竞争的影响。溶质扩散、溶剂流出和液滴内流动对模型系统产生影响。研究发现，壳层形成呈现出波动的特征，其中溶解物质在液滴表面的初始沉淀受到抑制，成核颗粒周期性地分散，直到壳层变得足够坚固以承受内部循环。这些内部效应取决于液滴大小，对较大的液滴更为明显。也就是说，颗粒的相行为和物理性质是雾化液滴大小的函数。基于这项研究的深入理解将为在目标设计空间中运行的优化单元提供参考。这将实现更好的产品质量控制，并最大限度地减少在早期阶段与商业规模过程开发中观察到的差异。
