Hot-melt extrusion

Hot-melt extrusion of API-particle-loaded polymer composites for pharmaceutical additive manufacturing processes

Elucidation of the process-structure relationships of API-particle-loaded polymer composites in hot-melt extrusion processes.

Sponsor: German Research Foundation (DFG)

Contact person: Johannes Lang

Summary of the project:

Hot-melt extrusion (HME) is a preferred process step in the pharmaceutical industry and research for the solvent-free production of solid (intermediate) products. In recent years, it has become particularly important for producing intermediates for melt-based 3D printing. This approach is being researched intensively because it enables the production of individualised dosage forms in terms of active pharmaceutical ingredient (API) dosage and release. To achieve the greatest possible dosage flexibility in additive manufacturing and to enable the production of individual combination preparations, it is essential to maximise the concentration of API in the intermediates produced by hot-melt extrusion.
During hot-melt extrusion, the API is embedded in a polymeric matrix to produce intermediates for 3D printing. Due to intermolecular interactions between the API and the polymer, as well as the increased temperature during processing, it is possible to dissolve the API in the polymeric matrix and obtain an amorphous dispersion. However, as the concentration of the API increases, complete dissolution of the API in the polymer can no longer be ensured, meaning that the API is partially present in particulate form during processing and in the solidified product. This poses challenges in terms of the mechanical properties of the intermediates and the subsequent 3D printing of the final dosage forms. Moreover, the process chain of HME and 3D printing involves repeated melting and shearing which can result in a change in the dispersion state of the API due to the partial solubility of the API within the polymer matrix.
Accordingly, the overarching aim of this research project is to establish material–process–structure–property relationships for complex, partially soluble particle-loaded polymer composites. To this end, innovative methods such as melt capillary rheology and Raman microscopy are specifically employed to analyse process conditions and product properties with high precision.

Goals and tasks at iPAT:

• Elucidation of process-structure relationships in the hot-melt-extrusion process and the downstream 3D printing process, to describe the dispersive properties of the API (particle size distribution, orientation)
• Establishment of capillary rheology for partially soluble, particle-loaded polymer melts, and testing its significance in process-structure relationships
• Establishment of structure-property relationships describing the influence of API dispersity on the mechanical properties and properties relevant for further processing
• Derivation of a two-stage population balance model to describe the development of the API’s particle size distribution along the process chain