Pharmaceutical Research and Technology Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka, Japan.
J Pharm Pharmacol. 2014 Feb;66(2):218-31. doi: 10.1111/jphp.12085. Epub 2013 May 28.
The goal of this investigation was to qualify the DSM Xplore Pharma Micro Extruder as a formulation screening tool for early-stage hot-melt extrusion.
Dispersive and distributive mixing was investigated using soluplus, copovidone or basic butylated methacrylate copolymer with sodium chloride (NaCl) in a batch size of 5 g. Eleven types of solid dispersions were prepared using various drugs and carriers in batches of 5 g in accordance with the literature.
The dispersive mixing was a function of screw speed and recirculation time and the particle size was remarkably reduced after 1 min of processing, regardless of the polymers. An inverse relationship between the particle size and specific mechanical energy (SME) was also found. The SME values were higher than those in large-scale extruders. After 1 min recirculation at 200 rpm, the uniformity of NaCl content met the criteria of the European Pharmacopoeia, indicating that distributive mixing was achieved in this time. For the solid dispersions preparations, the results from different scanning calorimetry, powder X-ray diffractometry and in-vitro dissolution tests confirmed that all solid-dispersion systems were successfully prepared.
These findings demonstrated that the extruder is a useful tool to screen solid-dispersion formulations and their material properties on a small scale.
本研究旨在将 DSM Xplore Pharma Micro Extruder 鉴定为用于早期热熔挤出的配方筛选工具。
使用 5g 批次的 Soluplus、共聚维酮或碱性丁基甲基丙烯酸酯共聚物与氯化钠（NaCl）对分散混合和分布混合进行了研究。根据文献，使用各种药物和载体以 5g 批次制备了 11 种固体分散体。
分散混合是螺杆速度和再循环时间的函数，无论聚合物如何，处理 1 分钟后粒径显著减小。还发现粒径与比机械能（SME）呈反比关系。SME 值高于大型挤出机的值。在 200rpm 下再循环 1 分钟后，NaCl 含量的均匀性符合欧洲药典的标准，表明在此时间内实现了分布混合。对于固体分散体的制备，来自不同差示扫描量热法、粉末 X 射线衍射法和体外溶解试验的结果证实所有固体分散系统都成功制备。
这些发现表明，该挤出机是一种有用的工具，可在小范围内筛选固体分散体配方及其材料性能。
