Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Mithushan Soundaranathan; Mohammed Al-Sharabi; Thomas Sweijen; Prince Bawuah; J. Axel Zeitler; S. Majid Hassanizadeh; Kendal Pitt; Blair F. Johnston; Daniel Markl

doi:10.3390/pharmaceutics15020489

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Mithushan Soundaranathan, Mohammed Al-Sharabi, Thomas Sweijen, Prince Bawuah, J. Axel Zeitler, S. Majid Hassanizadeh, Kendal Pitt, Blair F. Johnston, Daniel Markl^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, (Formula presented.) = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.

Original language	English
Article number	489
Pages (from-to)	1-19
Number of pages	19
Journal	Pharmaceutics
Volume	15
Issue number	2
DOIs	https://doi.org/10.3390/pharmaceutics15020489
Publication status	Published - Feb 2023

Bibliographical note

Funding Information:
This work was partially funded by the Scottish Research Partnership in Engineering (SRPe): National Manufacturing Institute Scotland—Industry Doctorate Programme (NMIS-IDP) (Project Award Number NMIS-IDP/005). In addition, the authors would like to thank the Future Continuous Manufacturing and Advanced Crystallisation Research Hub (Grant Ref. EP/P006965/1) and the Royal Society (Grant Ref. RSG/R2/180276) for funding this work. We would also like to thank Johnson Matthey and the U.K. Engineering and Physical Sciences Research Council (EPSRC) for funding this work.

Funding Information:
The authors would like to thank the Scottish Research Partnership in Engineering ( www.srpe.ac.uk ), the Scottish Funding Council ( www.sfc.ac.uk ), and the National Manufacturing Institute Scotland ( www.nmis.scot ) for their support of this work. The authors would like to acknowledge that this work was carried out in the CMAC National Facility supported by the UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant Ref. HH13054). S.M.H. acknowledges support from Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) under Germany’s Excellence Strategy—EXC 2075-390740016 and from the Stuttgart Center for Simulation Science (SimTech).

Publisher Copyright:
© 2023 by the authors.

Funding

This work was partially funded by the Scottish Research Partnership in Engineering (SRPe): National Manufacturing Institute Scotland—Industry Doctorate Programme (NMIS-IDP) (Project Award Number NMIS-IDP/005). In addition, the authors would like to thank the Future Continuous Manufacturing and Advanced Crystallisation Research Hub (Grant Ref. EP/P006965/1) and the Royal Society (Grant Ref. RSG/R2/180276) for funding this work. We would also like to thank Johnson Matthey and the U.K. Engineering and Physical Sciences Research Council (EPSRC) for funding this work. The authors would like to thank the Scottish Research Partnership in Engineering ( www.srpe.ac.uk ), the Scottish Funding Council ( www.sfc.ac.uk ), and the National Manufacturing Institute Scotland ( www.nmis.scot ) for their support of this work. The authors would like to acknowledge that this work was carried out in the CMAC National Facility supported by the UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant Ref. HH13054). S.M.H. acknowledges support from Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) under Germany’s Excellence Strategy—EXC 2075-390740016 and from the Stuttgart Center for Simulation Science (SimTech).

Keywords

discrete element method
pharmaceutical
pore size
swelling
tablet disintegration

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Cite this

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title = "Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets",

abstract = "Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, (Formula presented.) = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.",

keywords = "discrete element method, pharmaceutical, pore size, swelling, tablet disintegration",

author = "Mithushan Soundaranathan and Mohammed Al-Sharabi and Thomas Sweijen and Prince Bawuah and Zeitler, {J. Axel} and Hassanizadeh, {S. Majid} and Kendal Pitt and Johnston, {Blair F.} and Daniel Markl",

note = "Funding Information: This work was partially funded by the Scottish Research Partnership in Engineering (SRPe): National Manufacturing Institute Scotland—Industry Doctorate Programme (NMIS-IDP) (Project Award Number NMIS-IDP/005). In addition, the authors would like to thank the Future Continuous Manufacturing and Advanced Crystallisation Research Hub (Grant Ref. EP/P006965/1) and the Royal Society (Grant Ref. RSG/R2/180276) for funding this work. We would also like to thank Johnson Matthey and the U.K. Engineering and Physical Sciences Research Council (EPSRC) for funding this work. Funding Information: The authors would like to thank the Scottish Research Partnership in Engineering ( www.srpe.ac.uk ), the Scottish Funding Council ( www.sfc.ac.uk ), and the National Manufacturing Institute Scotland ( www.nmis.scot ) for their support of this work. The authors would like to acknowledge that this work was carried out in the CMAC National Facility supported by the UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant Ref. HH13054). S.M.H. acknowledges support from Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) under Germany{\textquoteright}s Excellence Strategy—EXC 2075-390740016 and from the Stuttgart Center for Simulation Science (SimTech). Publisher Copyright: {\textcopyright} 2023 by the authors.",

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AU - Hassanizadeh, S. Majid

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AU - Johnston, Blair F.

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N2 - Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, (Formula presented.) = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.

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Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Abstract

Bibliographical note

Funding

Keywords

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