Continuous Isolation of Particles with Varying Aspect Ratios up to Thin Needles Achieving Free-Flowing Products

Claas Steenweg,Kerstin Wohlgemuth,Jonas Habicht

doi:10.3390/cryst12020137

Abstract

The continuous vacuum screw filter (CVSF) for small-scale continuous product isolation of suspensions was operated for the first time with cuboid-shaped and needle-shaped particles. These high aspect ratio particles are very common in pharmaceutical manufacturing processes and provide challenges in filtration, washing, and drying processes. Moreover, the flowability decreases and undesired secondary processes of attrition, breakage, and agglomeration may occur intensively. Nevertheless, in this study, it is shown that even cuboid and needle-shaped particles (l-alanine) can be processed within the CVSF preserving the product quality in terms of particle size distribution (PSD) and preventing breakage or attrition effects. A dynamic image analysis-based approach combining axis length distributions (ALDs) with a kernel-density estimator was used for evaluation. This approach was extended with a quantification of the center of mass of the density-weighted ALDs, providing a measure to analyze the preservation of the inlet PSD statistically. Moreover, a targeted residual moisture below 1% could be achieved by adding a drying module (Tdry = 60 °C) to the modular setup of the CVSF.

Highlights

The small-scale production of active pharmaceutical ingredients (APIs) has been traditionally performed in batch mode, including all process steps from raw material treatment to the final drug formulation [1,2,3]
We developed the modular continuous vacuum screw filter (CVSF) in our research group and patented this innovative apparatus in 2021 [27]
The objective of this study is to demonstrate the broad applicability of CVSF for particles with varying aspect ratios and mean particle sizes while maintaining particle size distribution (PSD) and reducing residual moisture to free-flowing particles

Summary

Introduction

The small-scale production of active pharmaceutical ingredients (APIs) has been traditionally performed in batch mode, including all process steps from raw material treatment to the final drug formulation [1,2,3]. The major benefits of these integrated processes are the elimination of batch-to-batch variability, an increase in capacity either through parallelization of units or through longer plant run times, and a shorter time-to-market [5,6,11,12,13,14]. The latter arises with the opportunity to directly use the equipment designed in the research and development of a small-scale apparatus concept. Preserving the produced quality attributes is a crucial requirement for all subsequent isolation steps, namely, filtration, washing, and drying to achieve free-flowing particles usable for secondary processing

Objectives

Methods

Results

Conclusion