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压片用硅化微晶纤维素的拉伸强度与崩解:颗粒间结合的影响

Tensile strength and disintegration of tableted silicified microcrystalline cellulose: influences of interparticle bonding.

作者信息

Kachrimanis Kyriakos, Nikolakakis Ioannis, Malamataris Stavros

机构信息

Department of Pharmaceutical Technology, School of Pharmacy, University of Thessaloniki, Thessaloniki 54124, Greece.

出版信息

J Pharm Sci. 2003 Jul;92(7):1489-501. doi: 10.1002/jps.10403.

Abstract

The effects of some material variables (particle size and moisture content) on the tensile strength and disintegration time of tableted standard microcrystalline cellulose (MCC, Avicel) and a silicified brand (SMCC, Prosolv) were studied. Three particle size fractions were employed, after equilibration in three levels of environmental relative humidity (RH%), and the tensile strength and disintegration time were determined at different levels of total tablet porosity or packing fraction (p(f)). The MCC grade or silicification affects the moisture sorption and the packing during tapping as well as the particle deformation (yield pressure, P(y)) during tableting. There was a slight increase in the tensile strength but a marked increase in the disintegration time of Prosolv compared with Avicel in the p(f) range 0.7-0.9, which corresponds the range for pharmaceutical tablets. These increases are explained in terms of the range and magnitude of the interparticle forces developed and the interparticle separation. Despite the higher moisture content of Prosolv after equilibration compared with Avicel, compression of Prosolv results in higher P(y), in tablets of higher energy of interparticle bonding, longer interparticle separation, and extended disintegration compared with Avicel. The incorporated SiO(2) is thought to play the role of barrier or sink for the moisture sorbed, but only for RH up to 52%, which is a moisture content range less than twice that of tightly bound water. At higher RH (72%), the incorporated SiO(2) does not increase the P(y), but reduces the energy of interparticle bonding and the interparticle separation because of its probable saturation. The latter, in turn, results in more extended disintegration times due to reduced uptake of water into the tablets and to the probable reduction of water available for the deployment of the microcrystalline cellulose activity as disintegrant.

摘要

研究了一些材料变量(粒径和水分含量)对压片标准微晶纤维素(MCC,微晶纤维素)和硅化品牌(SMCC,Prosolv)的拉伸强度和崩解时间的影响。在三种环境相对湿度(RH%)水平下平衡后,采用了三种粒径级分,并在不同的总片剂孔隙率或堆积分数(p(f))水平下测定拉伸强度和崩解时间。MCC等级或硅化作用会影响水分吸附、压片过程中的堆积以及压片过程中的颗粒变形(屈服压力,P(y))。在p(f)范围为0.7 - 0.9(这与药物片剂的范围相对应)时,与微晶纤维素相比,Prosolv的拉伸强度略有增加,但崩解时间显著增加。这些增加可以根据颗粒间作用力的范围和大小以及颗粒间分离来解释。尽管平衡后Prosolv的水分含量高于微晶纤维素,但与微晶纤维素相比,Prosolv的压缩导致更高的P(y),片剂中颗粒间结合能更高,颗粒间分离更长,崩解时间延长。掺入的SiO₂被认为对吸附的水分起到屏障或吸收池的作用,但仅在RH高达52%时如此,这是一个水分含量范围,小于紧密结合水含量的两倍。在较高的RH(72%)下,掺入的SiO₂不会增加P(y),但由于其可能饱和,会降低颗粒间结合能和颗粒间分离。反过来,由于片剂对水的吸收减少以及可用于微晶纤维素作为崩解剂发挥作用的水可能减少,后者会导致崩解时间进一步延长。

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