An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion.
An investigation into the formations of the internal microstructures of solid dispersions prepared by hot melt extrusion.
复制标题
研究热熔挤出制备的固体分散体内部微观结构的形成。
DOI：
10.1016/j.ejpb.2020.08.018
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Alqahtani F
中科院分区：
文献类型：
--
作者：
Alqahtani F
热熔挤出（HME）是一种广泛用于药物固体分散体的制造工艺。HME制剂的复杂性和工艺中使用的辅料数量随着相关知识的进步而增加。然而，仍然明显缺乏理解的领域之一是挤出物的内部微观结构的控制。在热熔挤出的无定形固体分散体中，经常观察到由空隙组成的内部微观结构，而文献中没有系统地研究其原因。在这项研究中，我们研究了一系列因素，证明了它们对空隙形成的影响。这些因素包括配方中使用的材料类型（即药物、聚合物和添加剂）的影响、所用药物和添加剂的量、关键挤出加工参数、挤出机类型以及挤出前原材料的干燥。结果表明，适当的粘度和相分离颗粒的存在是形成空隙的必要条件。颗粒充当捕获的气泡的核，并且挤出期间混合物的粘度控制气泡的塌陷/逃逸。为了最大限度地减少空隙形成，本研究的结果表明，缓慢的螺杆速度、原材料的低水分含量、更少的颗粒和添加润滑剂（如低熔点脂质赋形剂）可能是有益的。本研究系统地研究了HME挤出物中空隙形成的机制，并产生了可用于管理此类空隙形成的新策略。
Hot melt extrusion (HME) is a widely used manufacturing process for pharmaceutical solid dispersions. The complexity of the HME formulations and the number of excipients used in the process are increasing with the advancement of the relevant knowledge. However, one of the areas that is still significantly lacking understanding is the control of internal microstructure of extrudates. Internal microstructure, consisting of voids, in hot melt extruded amorphous solid dispersions is often observed without the causes having been systemically investigated in the literature. In this study, we investigated a range of factors that demonstrated their impacts on the formation of the voids. These include the effect of the types of the materials (i.e. drug, polymer and additive) used in the formulation, the quantity of the drug and the additives used, the key extrusion processing parameters, the type of extruder, and the drying of the raw materials prior to extrusion. The results indicate that the appropriate viscosity and the presence of phase-separated particulates are essential for the formation of the voids. The particulates act as nuclei for the entrapped gas bubbles and the viscosity of the mixture during extrusion governs the collapse/escape of the bubbles. To minimise void formation, the results of this study indicate that slow screw speed, low moisture content of the raw materials, fewer particulates and the addition of lubricants, such as low melting lipid excipients, could be beneficial. This study systematically examines the mechanism of void formation in HME extrudates and generates new strategies that can be used to manage such void formations.
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