Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.
Eur J Pharm Biopharm. 2018 Apr;125:148-158. doi: 10.1016/j.ejpb.2018.01.017. Epub 2018 Jan 31.
To explain the rounding mechanism of extrudates by spheronization method, two main concepts are found in literature: one proposed by Rowe (1985) and one proposed by Baert et al. (1993). These concepts are based on wet extrusion-spheronization method using microcrystalline cellulose as mains excipient. However, there are no concepts for the spheronization mechanism of extrudates based on solid lipids as spheronization aid. Therefore, the aim of this study is to systematically investigate the mechanism of pellet formation of lipid based extrudates by lipid spheronization method. Different lipid based extrudate formulations were spheronized and particle size distribution and shape of the pellets, at each minute of the process, were characterized. Additionally, visual investigations of the morphological alterations were performed by optical and scanning electron microscopy. Two main material temperature phases were identified as presenting important influence on the pellet formation during the process: (1) a "brittle phase", where the extrudates are broken into smaller particles and (2) a "plastic phase", where the material starts to partially melt, allowing the particles to deform. By the same token, different morphological stages, from cylindrical rods to sphere-shaped passing through a dumbbell-shaped particle, were observed and showed to be highly dependent on temperature and process time. Moreover, a new particle shape, defined as "two-spheres", was recognized and a sequential material overlapping (covering) phenomenon was identified. This particular dislocation of material, from the edges to the central region of the particles (increasing their mean diameter), was recognized at longer process times and led to the formation of a smooth surface and the final spherical shape. At the end, a new concept of pellet formation from lipid extrudates is presented considering the observed changes in the morphology and particle size of the pellets during the spheronization process.
为了解释通过滚圆法挤出物的造粒机制，文献中发现了两个主要概念：一个是由 Rowe（1985 年）提出的，另一个是由 Baert 等人（1993 年）提出的。这些概念基于使用微晶纤维素作为主要赋形剂的湿挤出-滚圆法。然而，对于基于固体脂质作为滚圆助剂的挤出物的滚圆机制，尚无相关概念。因此，本研究的目的是系统研究基于脂质的挤出物通过脂质滚圆法形成颗粒的机制。对不同的基于脂质的挤出物配方进行滚圆，并在该过程的每一分钟对颗粒的粒径分布和形状进行表征。此外，还通过光学显微镜和扫描电子显微镜对形态变化进行了直观的观察。确定了两个主要的材料温度阶段，它们对过程中颗粒形成具有重要影响：（1）“脆性阶段”，在此阶段挤出物会破裂成较小的颗粒；（2）“塑性阶段”，在此阶段材料开始部分熔化，允许颗粒变形。同样，观察到了从圆柱形棒到球形再到哑铃形颗粒的不同形态阶段，并且发现它们高度依赖于温度和过程时间。此外，还识别出一种新的颗粒形状，称为“双球体”，并发现了一种连续的材料重叠（覆盖）现象。这种材料从颗粒边缘到中心区域的特殊错位（增加其平均直径）仅在较长的过程时间中被识别，从而导致形成光滑的表面和最终的球形形状。最后，考虑到在滚圆过程中颗粒的形态和粒径的观察到的变化，提出了一种新的基于脂质挤出物的颗粒形成概念。
