The Impact of Binders on Formulation Design in a Continuous Pharmaceutical Manufacturing Process based on Twin Screw Wet Granulation

Promovendus/a: Lise Vandevivere

Promotor(en): Prof. dr. Chris Vervaet, Prof. dr. Valérie Vanhoorne

Limited knowledge was available about the impact of the binder on formulation design in a continuous twin screw wet granulation process. Therefore, the overall objective of this thesis was to generate fundamental insight into the influence of different binder types (i.e. native starches as well as conventional and novel binders), and binder attributes on intermediate and final drug product properties, and on process performance in a continuous twin screw wet granulation process. The knowledge acquired during this project supports a rational and systematic formulation design for continuous wet granulation processes. The overall conclusion of the thesis was that proper binder selection in formulation design should focus on the binder requiring the lowest liquid amount for efficient granule production, taking granule breakage during transfer of wet granules to the dryer of a continuous manufacturing line into account. This lower liquid requirement implies a shorter drying time to obtain sufficiently dry granules at the end of a drying cycle, speeding up the overall drug production time and making the process more efficient. As the binder attributes that are key to result in high binder effectiveness for a poorly and highly soluble formulation were identified, rational binder selection for continuous twin screw granulation can be performed during early formulation development. Next to the binder, other formulation properties (filler) and process parameters (screw configuration) can be adopted to limit the liquid requirements of the formulation.