Emerging technologies for the non-invasive characterization of physical-mechanical properties of tablets

Abstract

The density, porosity, breaking force, viscoelastic properties, and the presence or absence of any structural defects or irregularities are important physical-mechanical quality attributes of popular solid dosage forms like tablets. The irregularities associated with these attributes may influence the drug product functionality. Thus, an accurate and efficient characterization of these properties is critical for successful development and manufacturing of a robust tablets. These properties are mainly analyzed and monitored with traditional pharmacopeial and non-pharmacopeial methods. Such methods are associated with several challenges such as lack of spatial resolution, efficiency, or sample-sparing attributes. Recent advances in technology, design, instrumentation, and software have led to the emergence of newer techniques for non-invasive characterization of physical-mechanical properties of tablets. These techniques include near infrared spectroscopy, Raman spectroscopy, X-ray microtomography, nuclear magnetic resonance (NMR) imaging, terahertz pulsed imaging, laser-induced breakdown spectroscopy, and various acoustic- and thermal-based techniques. Such state-of-the-art techniques are currently applied at various stages of development and manufacturing of tablets at industrial scale. Each technique has specific advantages or challenges with respect to operational efficiency and cost, compared to traditional analytical methods. Currently, most of these techniques are used as secondary analytical tools to support the traditional methods in characterizing or monitoring tablet quality attributes. Therefore, further development in the instrumentation and software, and studies on the applications are necessary for their adoption in routine analysis and monitoring of tablet physical-mechanical properties.

Robustness of a continuous direct compression line against disturbances in feeding

“…Spectroscopic techniques, such as near-infrared (NIR) and Raman spectroscopy, are some of the usual PAT tools that can be implemented to continuous processes (Alam et al, 2017;De Beer et al, 2008;De Leersnyder et al, 2018;Goodwin et al, 2018;Järvinen et al, 2013;Martínez et al, 2013;Nagy et al, 2017). Both techniques have also proven their benefits as off-and at-line measurements compared to wet chemistry analysis as the measurements can be performed without time-consuming sample preparation, allowing to analyze larger amounts of samples (Bonawi-tan and Williams, 2004;Dave et al, 2017;Paudel et al, 2015). NIR-chemical imaging (NIR-CI) is a further application of NIR that has been used to monitor final tablets (Khorasani et al, 2015;Wahl et al, 2017).…”

Morphological Analysis of Spherical Adsorptive Carbon Granules Using Three-Dimensional X-Ray Micro-computed Tomography

“…Thus, in this study the applicability of micro-computed tomography (CT) analysis in determining the morphology of particulate carbon granules was studied. [7][8][9][10][11][12][13][14]…”

Impact breakage of pharmaceutical tablets

“…In manufacturing tablets, the intention is not to maximise strengtha guide tensile strength of 1.5 -2.5 MPa is recommended by Stricker (1987) since this may impede disintegration in the digestive system, however it is necessary to have sufficiently robust tablets to prevent excessive attrition during handling of tablets in production and by the end user. A wide range of noninvasive techniques for analysis of tablet properties were reviewed by Dave et al (2017), with a number of soundwave-based methods identified for characterisation of tablet mechanical properties. These methods are used in a supportive manner in some instances, however analytical efficiency and operational complexity are cited as current barriers to widespread adoption.…”