Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process.

Lise Vandevivere,Cedrine De Backere,Olaf Häusler,Valérie Vanhoorne,Chris Vervaet,Thomas De Beer,Maxine Vangampelaere,Christoph Portier

doi:10.3390/pharmaceutics13020210

Lise Vandevivere, Cedrine De Backere + Show 6 more

Open Access

https://doi.org/10.3390/pharmaceutics13020210

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Journal: Pharmaceutics	Publication Date: Feb 3, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Ghent University, Roquette Frères (France)

Abstract

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

Highlights

The pharmaceutical industry is undergoing a gradual switch from batch to continuous manufacturing caused by multiple drivers, including reduction of cost, improved process efficiency, better control strategies, and lowering the environmental footprint [1,2,3,4,5]
Transition to continuous manufacturing is often based on the same formulation as used for batch processing in order to avoid additional studies [6]
Continuous Twin-screw granulation (TSG) requires minimum effort for scale-up, as batch sizes are determined by adjusting the total process time, saving time and costs

Summary

Introduction

Transition to continuous manufacturing is often based on the same formulation as used for batch processing in order to avoid additional studies [6]. As batch processing is fundamentally different from continuous processing (e.g., material residence time), materials are not necessarily suitable for both processing techniques [7]. The suitability of different materials for continuous manufacturing needs to be investigated. Twin-screw granulation (TSG) has proven its efficacy in continuous solid-dosage manufacturing, as this technique allows continuous production of granules while offering flexibility towards granule properties [8,9,10,11,12,13]. Continuous TSG requires minimum effort for scale-up, as batch sizes are determined by adjusting the total process time, saving time and costs. To the process parameters (e.g., screw speed, material throughput, barrel temperature), product quality is strongly influenced by the formulation variables

Methods

Results

Conclusion