About the Project
The compaction of powder is highly complex, but at the same time its understanding is crucial, especially in manufacturing pharmaceutical tablets as it compresses and consolidates the particles to form interparticulate bonds and pores. The pores in a tablet directly affect the rate at which the physiological fluids enter the tablet, leading to swelling of the particles and eventually causing the break-up of the compact into smaller agglomerates. The size of the disintegrated particles/agglomerates then drives the dissolution rate of the drug. These mechanisms are strongly interconnected as the swelling of particles dynamically changes the internal pore structure which influences the liquid imbibition process. The performance of a tablet can thus only be understood and optimised by considering the interconnection of every step involved in the disintegration and dissolution processes.
The project uses cutting-edge experimental technologies (e.g. X-ray computed nanotomography, terahertz pulsed imaging) and state-of-the art modelling approaches (discrete element modelling, pore-unit assembly approach) to address the two main objectives:
• Characterising particles, granular material and compacts that facilitate the development of models of every step involved in the disintegration and dissolution process.
• Developing a digital tablet to simulate the disintegration and dissolution process.
Research environment: The PhD student will be fully integrated into EPSRC (UK funding body) Future Continuous Manufacturing and Advanced Crystallisation Hub (CMAC). Training of the PhD student is aligned with the manufacturing research vision of CMAC that is informed by the needs of CMAC’s pharmaceutical industry partners GSK, AstraZeneca, Pfizer, Roche, Novartis, Lilly, Bayer & Takeda and technology partners. The PhD student will have access to a dedicated national network of world-class, state-of-the-art facilities including the £34M UK-RPIF funded CMAC National Facility.
Funding Notes
This project is fully funded by the National Manufacturing Institute for Scotland and the industry partners of CMAC (GSK, AstraZeneca, Pfizer, Roche, Novartis, Lilly, Bayer & Takeda). The student will have many opportunities to interact and collaborate with the pharmaceutical industry. Furthermore, the student will be fully integrated into CMAC to support her/his development, coordinate outputs and deliver the required outcomes over 4 years. This will also include intense formal training, targeted research skills development as well as participating in workshops.
References
References:
Markl, D., Zeitler, J.A., 2017. A Review of Disintegration Mechanisms and Measurement Techniques. Pharm Res 34, 890–917. doi:10.1007/s11095-017-2129-z
Sweijen, T., Hassanizadeh, S.M., Chareyre, B., Zhuang, L., 2018. Dynamic Pore‐Scale Model of Drainage in Granular Porous Media: The Pore‐Unit Assembly Method. Water Resources Research 74, 212. doi:10.1029/2017WR021769
Sweijen, T., Nikooee, E., Hassanizadeh, S.M., Chareyre, B., 2016. The Effects of Swelling and Porosity Change on Capillarity: DEM Coupled with a Pore-Unit Assembly Method. Transport in Porous Media 113, 207–226. doi:10.1007/s11242-016-0689-8
Sweijen, T., Chareyre, B., Hassanizadeh, S.M., Karadimitriou, N.K., 2017. Grain-scale modelling of swelling granular materials; application to super absorbent polymers. Powder Technology 318, 411–422. doi:10.1016/j.powtec.2017.06.015
Markl, D., Wang, P., Ridgway, C., Karttunen, A.-P., Bawuah, P., Ketolainen, J., Gane, P., Peiponen, K.-E., Zeitler, J.A., 2018. Resolving the rapid water absorption of porous functionalised calcium carbonate powder compacts by terahertz pulsed imaging. Chemical Engineering Research and Design 132, 1082–1090. doi:10.1016/j.cherd.2017.12.048
Markl, D., Yassin, S., Wilson, D.I., Goodwin, D.J., Anderson, A., Zeitler, J.A., 2017. Mathematical modelling of liquid transport in swelling pharmaceutical immediate release tablets. Int J Pharm 526, 1–10. doi:10.1016/j.ijpharm.2017.04.015
Markl, D., Sauerwein, J., Goodwin, D.J., van den Ban, S., Zeitler, J.A., 2017. Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements. Pharm Res 34, 1012–1022. doi:10.1007/s11095-017-2108-4
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