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Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Ridgway, Cathy 
van den Ban, Sander 
Goodwin, Daniel J 

Abstract

Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, Sa, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The Sa parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The Sa parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product.

Description

Keywords

Anisotropy, Disintegration, Microstructure, Pharmaceutical tablet, Pore structure, Terahertz, Anisotropy, Calcium Carbonate, Cellulose, Chemistry, Pharmaceutical, Excipients, Particle Size, Porosity, Powders, Tablets, Tensile Strength, Terahertz Spectroscopy

Journal Title

Int J Pharm

Conference Name

Journal ISSN

0378-5173
1873-3476

Volume Title

537

Publisher

Elsevier BV