Crystalline cellulose is a common inactive pharmaceutical additive. If this material can also be used to construct beads for the wet milling of pharmaceutical compounds, it could possibly address issues related to wear and contamination associated with zirconia and polyethylene beads. In this study, the model drug phenytoin was milled with spherical crystalline cellulose (SCC) in liquid nitrogen. The particle size of the milled product was found to be comparable to that obtained using zirconia beads, verifying the feasibility of using SCC beads for this purpose. Using a design of experiment approach, the bead amount, agitation speed, and milling time were all determined to have a significant effect on the milled particle size, giving a D50 value as low as 0.3 μm. No breakage of the SCC beads was observed during the milling process in durability tests under conditions that will degrade spherical D-mannitol beads, showing that this material exhibits sufficient durability. In addition, the variation in elastic modulus between beads was minimal. Because SCC is commercially available and easy to handle, the present wet milling technique is considered to have potential applications to the manufacture of pharmaceuticals on an industrial scale, as it shows sufficient milling capability and durability.

中文翻译：

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球形结晶纤维素珠的低温研磨：一种无污染且具有安全意识的技术。

结晶纤维素是常见的非活性药物添加剂。如果这种材料也可用于构建用于药物化合物湿磨的微珠，则可能解决与氧化锆和聚乙烯微珠相关的磨损和污染相关的问题。在这项研究中，将模型药物苯妥英钠与球状结晶纤维素（SCC）在液氮中研磨。发现研磨产物的粒度与使用氧化锆珠获得的粒度相当，证实了使用SCC珠用于此目的的可行性。使用实验方法设计，可以确定珠粒量，搅拌速度和研磨时间均对研磨后的粒径有显着影响，D50值低至0.3μm。在将球形D-甘露醇珠降解的条件下进行的耐久性试验中，在碾磨过程中未观察到SCC珠的破裂，表明该材料具有足够的耐久性。另外，珠之间的弹性模量的变化最小。因为SCC是可商购的并且易于处理，所以本湿磨技术被认为具有工业规模的药物制造潜力，因为它具有足够的研磨能力和耐用性。