喷雾干燥制备微粒的表面组分形成机理研究

Surface composition of spray dried microparticles is resulted from precursor migrating behaviors during droplet formation and evaporation, with dependence on both precursor properties and drying conditions, which not only determines particle characteristics, such as size, density, morphology and texture, but also powder wettability and re-dissolubility. Therefore, understanding formation mechanism of the microparticle surface composition is one of the key issues in spray drying related research and product quality control. However, the conventional spray drying technology usually suffers from varied particle properties and functionalities in a single sample batch, rendering difficulties in precisely correlating processing parameters with particle characteristics. To overcome such drawback, this study proposes to utilize a novel micro-fluidic jet spray drier capable of producing microparticles with uniform characteristics to investigate the effects of precursor size, solubility and surface activity on particle surface composition under different drying conditions. A series of two-component precursor liquids will be selected to avoid more complexities possibly caused by multiple components. Towards the uncertainty over migrating direction to droplet surface or centre for the surface active molecule, spray freeze drying will be used to acquire the surface composition of the droplet prior to evaporation. In comparison to surface composition of the spray dried microparticles, the possible surface enrichment due to the precursor surface activity during such two processes of droplet formation and evaporation will be clarified. Combined with the effects of precursor size, solubility, surface activity and spray drying condition, a theory model is aimed to be set-up for the formation mechanism for microparticle surface composition. The outcome of this project is expected to provide important theoretical basis and experimental support for the rational design and control over surface composition of spray dried product.

喷雾干燥微粒的表面组分取决于前驱物在液滴形成及蒸发过程中的迁移行为，受前驱物性质和喷雾干燥条件的共同作用，不仅是影响微粒尺寸、密度、形貌等性质的重要因素，而且决定了产品诸多重要性能，例如润湿性、复溶性等。因此，微粒表面组分的形成机理是喷雾干燥技术研究及产品质量控制中的关键问题之一。本项目为克服传统喷雾干燥同批产品微粒的性质差异化所造成的弊端，将使用一种新型的微流体喷雾干燥塔，利用其能够制备性质均一微粒的优势，针对二元体系前驱液，研究前驱物尺寸、溶解度、表面活性在不同干燥条件下对微粒表面组分的影响规律；针对表面活性分子迁移行为的不确定性，利用喷雾冷冻获取液滴表面组分数据，与喷雾干燥微粒比较，分步考察表面活性分子在液滴形成且未蒸发前和液滴蒸发两个过程中的表面富集程度，综合前驱物尺寸和溶解度的作用规律，构建影响微粒表面组分的理论模型，为实现喷雾干燥微粒表面组分的设计与调控提供理论依据和实验支持。

喷雾干燥是工业中最重要的把液体干燥制成粉末产品的技术之一，由于其干燥速率快、生产能力大、自动化程度高等优势，已被广泛应用于诸如医药、食品、吸附剂、催化剂等多种类型产粉状品的生产和加工领域。为进一步提升喷雾干燥产品的质量及附加值，尤为重要的是如何通过配方筛选和工艺参数调节，有效调控产品颗粒的物化性质，以实现最优产品功能。然而，在液滴快速蒸发过程中，配方物质的迁移行为及多尺度组装成粒过程极其复杂，这也是高质量喷雾干燥产品的研发和生产所面临的关键挑战。.本项目利用一种原创的微流控喷雾干燥设备，借助其制备微粒的物化性质均一可控的优势，避免了传统喷雾干燥技术中同批样品微粒性质差异化的弊端，能够有效建立过程工艺参数与微粒物化性质间的直接对应关系，为研究喷雾干燥颗粒结构的形成机理与调控机制提供了有力支撑。在基础理论方面，探究了配方物质的分子尺寸、溶解度、表面活性等性质，以及喷雾干燥条件对颗粒微纳结构的影响机理，并构建了一套独特的多尺度数值模拟方法，能够较为准确的预测产品颗粒特性，为实现喷雾干燥颗粒结构的精准设计与调控建立了良好的理论基础。在应用基础研究方面，围绕控释药物颗粒、高生物活性颗粒、吸附剂微粒等产品应用领域，通过有效调节喷雾干燥颗粒的微纳结构，并与之相关的性能指标进行了系统性对比，揭示了决定产品颗粒功能的关键构效关系，将十分有助于高质量喷雾干燥产品的研发和生产。