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粉状纤维素与碳酸镁的共处理:直接压片与辊压/干法制粒后压片

Coprocessing of powdered cellulose and magnesium carbonate: direct tableting versus tableting after roll compaction/dry granulation.

作者信息

Freitag Franziska, Runge Jürgen, Kleinebudde Peter

机构信息

Institute of Pharmaceutics and Biopharmaceutics, Martin-Luther-University Halle-Wittenberg, Halle-Wittenberg, Germany.

出版信息

Pharm Dev Technol. 2005;10(3):353-62. doi: 10.1081/pdt-65667.

Abstract

Mixtures of magnesium carbonate (MC) with three types of powdered cellulose (M80, P290, A300) were tableted directly or after roll compaction/dry granulation. The fraction of powdered cellulose in the mixture was varied from 0% to 25% (w/w). The properties of the granules, blends, and their corresponding tablets were analyzed. Granules with a low amount of A300 showed the best flow properties, whereas the fibrous shape of the binding agents M80 and P290 impaired the free flow. Heckel plots showed clearly the different behavior of powdered cellulose in blends and granules during the tableting process. The Heckel-Plots for pure MC powder and granulated MC (MCgr) were similar. Increasing the fraction of powdered cellulose resulted in a fan-shaped set of curves, which is a reflection of an increased densification. Physical mixtures of all three powdered celluloses and granulated mixtures of M80 resulted in a higher densification compared with pure MC. In contrast, the granulated mixtures of P290 and A300 resulted in a diminished densification during tableting, which means that the coprocessed mixtures behaved differently during tableting compared with the physical mixtures. The curves were lower than those of pure MC and MCgr most pronounced at a fraction of 5% powdered cellulose. The tablet pore structure was evaluated by mercury porosimetry. The addition of P290 and A300 to the dry granules resulted in tablets with a higher fraction of smaller pores. Comparably high values for tablet tensile strength and low friability resulted from this special tablet structure. Roll compacted/dry granulated MC, coprocessed with 5% of P290 or A300, seems to be a promising excipient for direct compression. This coprocessed product combines good flow and tablet properties, and is superior to pure MC or a physical mixture of MC and PC.

摘要

将碳酸镁(MC)与三种类型的粉状纤维素(M80、P290、A300)的混合物直接压片,或在滚压/干法制粒后压片。混合物中粉状纤维素的比例从0%变化到25%(w/w)。分析了颗粒、共混物及其相应片剂的性质。含有少量A300的颗粒表现出最佳的流动性,而粘合剂M80和P290的纤维形状则妨碍了自由流动。Heckel图清楚地显示了压片过程中粉状纤维素在共混物和颗粒中的不同行为。纯MC粉末和造粒MC(MCgr)的Heckel图相似。增加粉状纤维素的比例会导致一组扇形曲线,这反映了致密化程度的增加。与纯MC相比,所有三种粉状纤维素的物理混合物以及M80的造粒混合物导致更高的致密化。相比之下,P290和A300的造粒混合物在压片过程中导致致密化程度降低,这意味着共处理混合物在压片过程中的行为与物理混合物不同。在粉状纤维素比例为5%时,曲线比纯MC和MCgr的曲线低得最为明显。通过压汞法评估片剂的孔隙结构。向干颗粒中添加P290和A300会使片剂具有更高比例的小孔。这种特殊的片剂结构导致片剂具有相当高的抗张强度值和低脆碎度。与5%的P290或A300共处理的滚压/干法制粒MC似乎是直接压片的一种有前景的辅料。这种共处理产品兼具良好的流动性和片剂性质,并且优于纯MC或MC与PC的物理混合物。

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