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

Daniel Markl, Prince Bawuah, Cathy Ridgway, Sander van den Ban, Daniel J.Goodwin, Jarkko Ketolainen, Patrick Gane, Kai-Erik Peiponen,  J. Axel Zeitler

https://www.sciencedirect.com/science/article/pii/S0378517317311730

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.

Abstract-Analysis of anisotropic pore structures using terahertz spectroscopy and imaging

Daniel Markl,  Cathy Ridgway, Prince Bawuah,  Patrick Gane,  Jarkko Ketolainen,  Kai-Erik Peiponen,  J Axel Zeitler

http://ieeexplore.ieee.org/document/8066929/

This study demonstrates the analysis of anisotropic pore structures of highly porous pharmaceutical powder compacts by combining terahertz time-domain spectroscopy and in-situ measurements of the liquid penetration using terahertz pulsed imaging.

Abstract-On the role of API in determining porosity, pore structure and bulk modulus of the skeletal material in pharmaceutical tablets formed with MCC as sole excipient

• Cathy Ridgway,  
• Prince Bawuah, 
• Daniel Markl, 
• J. Axel Zeitler, 
• Jarkko Ketolainen, 
• Kai-Erik Peiponen, 
• Patrick Gane, 

• ^a Omya International AG, CH-4665 Oftringen, Switzerland
• ^b Institute of Photonics, University of Eastern Finland, P.O. Box 111, FI-80101 Joensuu, Finland
• ^c Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, United Kingdom
• ^d School of Pharmacy, Promis Centre, University of Eastern Finland, P.O. Box 1617, FI-70211, Kuopio, Finland
• ^e Aalto University, Chemical Engineering, Bioproducts and Biosystems, FI-00076 Aalto, Helsinki, Finland
• 
  

http://www.sciencedirect.com/science/article/pii/S0378517317303393

The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties

Abstract-Optics-based compressibility parameter for pharmaceutical tablets obtained with the aid of the terahertz refractive index

Mousumi Chakraborty,  Cathy Ridgway, Prince Bawuah, Daniel Markl, Patrick A.C. Gane, Jarkko Ketolainen, J.Axel Zeitler, Kai-Erik Peiponen,

http://www.sciencedirect.com/science/article/pii/S037851731730279X

The objective of this study is to propose a novel optical compressibility parameter for porous pharmaceutical tablets. This parameter is defined with the aid of the effective refractive index of a tablet that is obtained from non-destructive and contactless terahertz (THz) time-delay transmission measurement. The optical compressibility parameter of two training sets of pharmaceutical tablets with a priori known porosity and mass fraction of a drug was investigated. Both pharmaceutical sets were compressed with one of the most commonly used excipients, namely microcrystalline cellulose (MCC) and drug Indomethacin. The optical compressibility clearly correlates with the skeletal bulk modulus determined by mercury porosimetry and the recently proposed terahertz lumped structural parameter calculated from terahertz measurements. This lumped structural parameter can be used to analyse the pattern of arrangement of excipient and drug particles in porous pharmaceutical tablets. Therefore, we propose that the optical compressibility can serve as a quality parameter of a pharmaceutical tablet corresponding with the skeletal bulk modulus of the porous tablet, which is related to structural arrangement of the powder particles in the tablet.