Inline Determination of Residence Time Distribution in Hot-Melt-Extrusion.

Jens Wesholowski,Markus Thommes,Andreas Berghaus

doi:10.3390/pharmaceutics10020049

Jens Wesholowski, Markus Thommes + Show 1 more

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https://doi.org/10.3390/pharmaceutics10020049

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Journal: Pharmaceutics	Publication Date: Apr 15, 2018
Citations: 31	License type: CC BY 4.0

Affiliation: TU Dortmund University, ColVisTec (Germany)

Abstract

In the framework of Quality-by-Design (QbD), the inline determination of process parameters or quality attributes of a product using sufficient process analytical technology (PAT) is a center piece for the establishment of continuous processes as a standard pharmaceutical technology. In this context, Twin-Screw-Extrusion (TSE) processes, such as Hot-Melt-Extrusion (HME), are one key aspect of current research. The main benefit of this process technology is the combination of different unit operations. Several of these sub-processes are linked to the Residence Time Distribution (RTD) of the material within the apparatus. In this study a UV/Vis spectrophotometer from ColVisTec was tested regarding the suitability for the inline determination of the RTD of an HME process. Two different measuring positions within a co-rotating Twin-Screw-Extruder were compared to an offline HPLC–UV as reference method. The obtained results were overall in good agreement and therefore the inline UV/Vis spectrophotometer is suitable for the determination of the RTD in TSE. An influence of the measuring position on repeatability was found and has to be taken into consideration for the implementation of PATs. An effect of the required amount of marker on process rheology is not likely due to the low Limit-of-Quantification (LoQ).

Highlights

In recent years, the pharmaceutical industry has had to deal with challenges related to the concept of Quality-by-Design (QbD) [1] and a shift of production focus from batch to continuous manufacturing
The aim of this study is to investigate the suitability of an inline UV/Vis-spectroscopy device for the Residence Time Distribution (RTD) determination of an HME process
The RTD was determined by adding a marker substance in the hopper of the extruder and measuring the Transmission Tr (Equation (1)) as response signal with respect to time t and the wavelength λ (Figure 5, left) at the die in two different measuring positions (Section 2.3)

Summary

Introduction

The pharmaceutical industry has had to deal with challenges related to the concept of Quality-by-Design (QbD) [1] and a shift of production focus from batch to continuous manufacturing. A typical application for this continuous, robust and cost-efficient process is the production of solid dispersions by Hot-Melt-Extrusion (HME) [2,3], where an active pharmaceutical ingredient (API) is dissolved and distributed within a molten matrix carrier. In such a process, various unit operations are combined in one step. Mechanism feeding, degassing and extruding have a crucial impact on the product homogeneity, uniformity and shape [4,5,6,7]. The screw configuration is a crucial variable on different sub–processes, e.g., for solvent–free salt preparation during extrusion, in combination with temperature [12]

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