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片剂的力学性能取决于纳米和微观尺度的粘附、润滑及结构。

Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure.

作者信息

Badal Tejedor Maria, Nordgren Niklas, Schuleit Michael, Rutland Mark W, Millqvist-Fureby Anna

机构信息

SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden; KTH Royal Institute of Technology, Division of Surface and Corrosion Science, Drottning Kristinas väg 51, SE-100 44 Stockholm, Sweden.

SP, Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden.

出版信息

Int J Pharm. 2015;486(1-2):315-23. doi: 10.1016/j.ijpharm.2015.03.049. Epub 2015 Apr 1.

Abstract

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture.

摘要

片剂是药物给药最方便的剂型。然而,尽管制造容易,但在生产过程中会出现诸如粉末粘附等问题。本研究展示了在不同压实条件下压制的、含有常用辅料(微晶纤维素(MCC)、乳糖、甘露醇、硬脂酸镁(Mg))的片剂的表面和结构特征。用扫描电子显微镜(SEM)、轮廓仪和原子力显微镜(AFM)进行片剂表面分析。用片剂硬度测试评估片剂的机械性能。当配方中存在硬脂酸镁时,AFM检测到的局部粘附力降低。此外,添加硬脂酸镁后,MCC等可塑性变形辅料的片剂强度显著降低。综合这些事实表明,硬脂酸镁会影响颗粒间的结合,从而影响弹性恢复。MCC辅料还表现出最高的硬度,这是高内聚性材料的特征。这是从使用AFM在纳米尺度上发现的MCC与亲水性探针之间相对较高的粘附力的角度进行讨论的。相比之下,乳糖和甘露醇等脆性材料的片剂强度不受硬脂酸镁的影响。因此,断裂发生在辅料颗粒内部而非颗粒边界,产生了以前未暴露于硬脂酸镁的新表面。这种未包覆的表面很可能会促进制造过程中与工具的粘附相互作用。

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