(342h) Using Discrete Element Model Technique to Design a Densification Process for a Lyophilized Pharmaceutical Powder Formulation

Powder flowability is an important attribute to consider while designing manufacturing processes for pharmaceutical solid dosage forms since it affects the die or capsule filling. Bulk powder properties, e.g., bulk density and particle size distribution affect the flow properties of the powder [1]. Pharmaceutical drug product formulations with low bulk densities or small particle size often have poor flow properties; hence the particles need to be engineered further so that the flowability improves.

This work presents a case study for densifying a lyophilized powder so that it can be efficiently encapsulated. Traditional methods for improving flow properties (e.g., wet granulation, roller compaction) are not applicable since lyophilized powders are sensitive to moisture and high temperature. Hence a mechanism using a densification piston was adapted. Examples of powder densification techniques using densification piston exists in other industries [2]. We adapted an approach where a densification piston was fitted at the outlet of a powder screw feeder. The piston applied a compressive force on the powder to form loose agglomerates of the powder particles and increase the powder bulk density, thus improving the powder flowability.

It is important to determine the magnitude of the compressive force to apply so that the bulk density of the powder is in an acceptable range that is amenable to encapsulation. The equipment configuration and settings determine the range of compressive forces that can be achieved. A discrete element model (DEM) was used to build the understanding and thus design the process. A qualitative DEM incorporating the Edinburgh Elastic Plastic Adhesion contact model [3] and representative model material properties was developed on EDEM (Altair EDEM). This work will highlight the model development and the outcome.

Acknowledgement: The work was done as part of a collaboration between Eli Lilly and Company and Altair EDEM when Callum Bruce was part of the EDEM team.

References

[1] D. Shah, K. Moravkar, D. Jha, V. Lonkar, P. Amin and S. Chalikwar, "A concise summary of powder processing methodologies for flow enhancement," Heliyon, vol. 9, no. 6, e16498, 2023.

[2] S. Obidzinski and J. Piekut, "Influence of speed of densification piston and particle size of densified material on the value of densifying pressures and pellets density," Journal of Research and Applications in Agricultural Engineering, vol. 60, no. 1, 63-68, 2015.

[3] S. Thakur, J. Morrissey, J. Sun, J. Chen and J. Ooi, "Micromechanical analysis of cohesive granular materials using the discrete element method with an adhesive elasto-plastic contact model," Granular Matter, vol. 16, 383-400, 2014.