Project for TUM PREP
Particle segregation during selective laser sintering (SLS) of pharmaceutical tablets: Experimental and discrete element method study
1. Motivation
Homogeneous mixing of multi-component powders represents a significant challenge across various industries. These challenges arise not only from differences in particle sizes, densities, and shapes, but also from the cohesion of particles, particularly in the pharmaceutical sector [1].
One of the most important additive manufacturing methods is Selective Laser Sintering (SLS), a unique thermal binding process that allows pharmaceutical powder particles to be fused together, enabling the layer-by-layer production of pharmaceutical tablets within a powder bed. Research on the application of SLS for producing different drug-loaded tablets began after its initial appearance in 2017 [2]. In this process, the homogeneous distribution of the multi-sized powder mixture plays a crucial role in the subsequent steps. Considering the minuscule proportions of predominantly fine active ingredients within a matrix of much larger components in tablets, such as drugs containing 5% paracetamol and 92% polyethylene oxide [3], the consequences of particle segregation can be severe. Furthermore, the inhomogeneity of the powder mixture might worsen after the spreading process. However, the behavior of particles throughout the entire process has not yet been thoroughly and systematically examined.
Pharmaceutical powders consist of solid particles, yet powder mixtures exhibit liquid-like behavior. For powder mixtures with very small particle sizes, cohesion plays a significant role. However, the mechanism of cohesive particles in various processes is not well understood. DEM simulations are state-of-the-art in this application area.
2. Research Objectives
The main aim of this TUM PREP project is to develop reasonable DEM simulation models that accurately replicates the spreading, melting, and binding process of cohesive powders.
Throughout the entire project period, theoretical considerations and numerical simulations are expected to enhance understanding of particle mixing, segregation, and spreading. The fundamental study on the particle mechanism and the results of powder relevant experiment and SLS-based 3D printing of tablets will be applied for further optimizing the preparation of pharmaceutical mixtures in SLS.
3. Work Packages
• Familiarization with the Discrete Element Method and one of following simulation tools: EDEM, Ansys Rocky and LIGGGHTS
• Experiment in labor with particle measurement, differential scanning calorimetry, UV spectroscopy and micro-CT.
• DEM simulation and development of API
4. Prerequisites
We are seeking students who have an interest in powder process engineering, work independently, and demonstrate meticulousness.
• Interest/experience in particle scale research, including experiment or simulation.
• Basic programming knowledge, e.g. C++, python
5. Reference
[1] A. Kottlan, B. J. Glasser, and J. G. Khinast, “Vibratory mixing of pharmaceutical powders on a single-tablet-scale,” Powder Technol., vol. 387, pp. 385–395, Jul. 2021, doi: 10.1016/j.powtec.2021.04.040.
[2] A. Awad, F. Fina, A. Goyanes, S. Gaisford, and A. W. Basit, “Advances in powder bed fusion 3D printing in drug delivery and healthcare,” Adv. Drug Deliv. Rev., vol. 174, pp. 406–424, Jul. 2021, doi: 10.1016/j.addr.2021.04.025.
[3] N. Wang, H. Shi, and S. Yang, “3D printed oral solid dosage form: Modified release and improved solubility,” J. Controlled Release, vol. 351, pp. 407–431, Nov. 2022, doi: 10.1016/j.jconrel.2022.09.023.
[4] E. Jakubowska and N. Ciepluch, “Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review,” Pharmaceutics, vol. 13, no. 11, p. 1909, Nov. 2021, doi: 10.3390/pharmaceutics13111909.
[5] Y. Tsunazawa, N. Soma, and M. Sakai, “DEM study on identification of mixing mechanisms in a pot blender,” Adv. Powder Technol., vol. 33, no. 1, p. 103337, Jan. 2022, doi: 10.1016/j.apt.2021.10.029.
