Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics.
Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics.
复制标题
多溶剂微滴蒸发：吸入药物喷雾干燥动力学的建模和测量。
DOI：
10.1007/s11095-019-2630-7
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发表时间：
2019
影响因子：
3.7
通讯作者：
Ordoubadi M
中科院分区：
文献类型：
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作者：
Ordoubadi M
目的研究含固体赋形剂的多溶剂微滴在喷雾干燥中的蒸发和微粒形成过程。各种水和乙醇共溶剂系统含有各种活性物质和赋形剂（倍氯米松，布地奈德，亮氨酸，和海藻糖）被认为是methodsNumerical方法被用来预测液滴蒸发速率和内部溶质转移，其结果验证和比较结果从两个独立的实验设置。特别是，电动平衡被用来测量的蒸发速率的多组分液滴和单分散液滴链设置收集干燥的微粒进一步的分析调查和ultramicross.ResultsThe数值结果被用来解释不同的颗粒形态干燥的解决方案在不同的共溶剂组合物。所获得的数值数据清楚地表明，控制干燥颗粒的一般形态的两个参数，即Péclet数和饱和度，可以在多溶剂液滴中随时间变化。这一事实使此类系统的产品开发复杂化。然而，这种额外的复杂性在我们定义为等组成点的地方消失了，当溶剂比例和液滴的其他组成相关性质在蒸发过程中保持恒定时，结论多溶剂系统的数值和实验分析表明，在等熵区附近的喷雾干燥，组成比简化了这种系统的设计和工艺开发。
PurposeEvaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered.MethodsNumerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy.ResultsThe numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation.ConclusionsNumerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.