How does the tableting process affect the quality of pharmaceutical tablets?

Описание: Presentation by Dr Prince Bawuah at the IFPAC 2021 virtual meeting (http://www.ifpacglobal.org/).

Insight into the impact of process variations in tablet processing on tablet disintegration by non-destructive at-line terahertz porosity sensing

Tablet porosity is a fundamental quality attribute which controls key mass transport mechanisms that govern disintegration behaviour and ultimately drug release and dissolution in a number of widely used oral solid dosage forms [1]. This study demonstrates the use of TeraSolve, a newly developed at-line PAT tool based on transmission terahertz spectroscopy, for fast and non-destructive measurement of tablet porosity and disintegration time [2-5]. At the example of batches of direct compressed immediate release ibuprofen tablets produced at different process conditions on a rotary tablet press we investigate the impact of varying processing conditions on the disintegration performance. For each batch the measurements of 250 tablets are used to obtain insights into the drug product quality variability at each process condition.

Our results show that the terahertz method is fast, robust and non-destructive and requires no chemometric methods to be employed. It allows to measure 250 tablets in less than 2.5 hours while destructive disintegration testing would take more than 60 hours measurement time alone for the same number of tablets. By testing a large number of samples outliers in tablet quality, potentially nonconforming product, can be clearly quantified and a unique opportunity for process understanding and quality assurance of the drug product is now available to pharmaceutical scientists. This may help establish opportunities for effective and reliable real-time release testing (RTRT) applications in the future [6].

[1] Markl, D. et al. (2017) J. Pharm. Sci. 106:1586-1595, https://doi.org/10.1016/j.xphs.2017.0....
[2] Bawuah, P. et al. (2014) Int. J. Pharm. 476:16-22, https://doi.org/10.1016/j.ijpharm.201....
[3] Markl, D. et al. (2018) Int. J. Pharm. 538:188-214, https://doi.org/10.1016/j.ijpharm.201....
[4] Markl, D. et al. (2017) Pharm. Res. 34:1012-1022, https://doi.org/10.1007/s11095-017-21....
[5] Bawuah, P. et al. (2021) J. Pharm. Sci., https://doi.org/10.1016/j.xphs.2020.1...
[6] Markl, D. et al. (2020) Int. J. Pharm., 582:119353 https://doi.org/10.1016/j.ijpharm.202...

Authors:

Prince Bawuah and J. Axel Zeitler
University of Cambridge, Department of Chemical Engineering and Biotechnology, UK, [email protected]

Mike Evans and Daniel Farrell
TeraView Limited, 1, Enterprise, Cambridge Research Park, CB25 9PD, Cambridge, UK

Ard Lura and Peter Kleinebudde
Heinrich-Heine-University, Institute of Pharmaceutics and Biopharmaceutics, Dusseldorf, Germany

Daniel Markl
University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Sciences, Glasgow, UK
EPSRC Future Manufacturing Research Hub for Continuous Manufacturing and Advanced Crystallisation (CMAC), University of Strathclyde, Technology and Innovation Centre, Glasgow, UK