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不同体积比的微晶纤维素 - 磷酸氢钙混合物对片剂压实及结构力学性能的影响

The Effect of Microcrystalline Cellulose-CaHPO Mixtures in Different Volume Ratios on the Compaction and Structural-Mechanical Properties of Tablets.

作者信息

Mohylyuk Valentyn, Paulausks Artūrs, Radzins Oskars, Lauberte Liga

机构信息

Laboratory of Finished Dosage Forms, Faculty of Pharmacy, Rīga Stradiņš University, LV-1007 Riga, Latvia.

Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, LV-1658 Riga, Latvia.

出版信息

Pharmaceutics. 2024 Mar 5;16(3):362. doi: 10.3390/pharmaceutics16030362.

DOI:10.3390/pharmaceutics16030362
PMID:38543256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10975345/
Abstract

Using microcrystalline cellulose (MCC) with plastic behaviour and calcium phosphate anhydrous (CaHPO) with brittle behaviour under compaction is very popular in the pharmaceutical industry for achieving desirable structural-mechanical properties of tablet formulations. Thus, mixtures of specific grades of MCC and CaHPO were tested in volume proportions of 100-0, 75-25, 50-50, 25-75, and 0-100 at a constant weight-by-weight concentration of sodium stearyl fumarate lubricant, utilizing a state-of-the-art benchtop compaction simulator (STYL'One Nano). Tablet formulations were prepared at 100, 150, 250, 350, 450, and 500 MPa, and characterized by tabletability profile, ejection force profile, proportion-tensile strength relationship, proportion-porosity relationship, pressure-displacement, and elastic recovery profiles, as well as by in-/out-of-die Heckel plots and yield pressures. Interestingly, the 25-75 formulation demonstrated a two-stage out-of-die Heckel plot and was additionally investigated with X-ray micro-computed tomography (µCT). By post-processing the µCT data, the degree of brittle CaHPO particles falling apart, along with the increasing compression pressure, was quantified by means of the surface area to volume (S/V) ratio. For the 25-75 formulation, the first stage (up to 150 MPa) and second stage (above the 150 MPa) of the out-of-die Heckel plot could be attributed to predominant MCC and CaHPO deformation, respectively.

摘要

在制药行业中,使用具有塑性行为的微晶纤维素(MCC)和在压实过程中具有脆性的无水磷酸钙(CaHPO)来实现片剂制剂所需的结构力学性能非常普遍。因此,在硬脂酰富马酸钠润滑剂的重量比浓度恒定的情况下,对特定等级的MCC和CaHPO混合物按体积比例100 - 0、75 - 25、50 - 50、25 - 75和0 - 100进行了测试,采用了最先进的台式压实模拟器(STYL'One Nano)。在100、150、250、350、450和500 MPa下制备片剂制剂,并通过可压性曲线、顶出力曲线、比例 - 拉伸强度关系、比例 - 孔隙率关系、压力 - 位移和弹性恢复曲线,以及通过模内/模外Heckel图和屈服压力来表征。有趣的是,25 - 75配方显示出两阶段的模外Heckel图,并另外用X射线微计算机断层扫描(µCT)进行了研究。通过对µCT数据进行后处理,借助表面积与体积(S/V)比量化了随着压缩压力增加而破碎的脆性CaHPO颗粒的程度。对于25 - 75配方,模外Heckel图的第一阶段(高达150 MPa)和第二阶段(高于150 MPa)可分别归因于主要的MCC和CaHPO变形。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/4c7f8a8009e6/pharmaceutics-16-00362-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/649b9a652ecb/pharmaceutics-16-00362-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/dc1d31b43acc/pharmaceutics-16-00362-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/717154ddcd4d/pharmaceutics-16-00362-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/8b5912a57d24/pharmaceutics-16-00362-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/104dea4e0e38/pharmaceutics-16-00362-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/14098a30753b/pharmaceutics-16-00362-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/4c7f8a8009e6/pharmaceutics-16-00362-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/649b9a652ecb/pharmaceutics-16-00362-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/dc1d31b43acc/pharmaceutics-16-00362-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/717154ddcd4d/pharmaceutics-16-00362-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/8b5912a57d24/pharmaceutics-16-00362-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/104dea4e0e38/pharmaceutics-16-00362-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/14098a30753b/pharmaceutics-16-00362-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fca9/10975345/4c7f8a8009e6/pharmaceutics-16-00362-g007.jpg

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