Process monitoring and visualization solutions for hot-melt extrusion: a review

Abstract

Objectives Hot-melt extrusion (HME) is applied as a continuous pharmaceutical manufacturing process for the production of a variety of dosage forms and formulations. To ensure the continuity of this process, the quality of the extrudates must be assessed continuously during manufacturing. The objective of this review is to provide an overview and evaluation of the available process analytical techniques which can be applied in hot-melt extrusion. Key Findings Pharmaceutical extruders are equipped with traditional (univariate) process monitoring tools, observing barrel and die temperatures, throughput, screw speed, torque, drive amperage, melt pressure and melt temperature. The relevance of several spectroscopic process analytical techniques for monitoring and control of pharmaceutical HME has been explored recently. Nevertheless, many other sensors visualizing HME and measuring diverse critical product and process parameters with potential use in pharmaceutical extrusion are available, and were thoroughly studied in polymer extrusion. The implementation of process analytical tools in HME serves two purposes: (1) improving process understanding by monitoring and visualizing the material behaviour and (2) monitoring and analysing critical product and process parameters for process control, allowing to maintain a desired process state and guaranteeing the quality of the end product. Summary This review is the first to provide an evaluation of the process analytical tools applied for pharmaceutical HME monitoring and control, and discusses techniques that have been used in polymer extrusion having potential for monitoring and control of pharmaceutical HME.

A novel transflectance near infrared spectroscopy technique for monitoring hot melt extrusion

“…The FDA now encourages process innovation in the pharmaceutical industry through better process understanding achieved by adopting Quality by Design (QbD) and PAT (FDA Guidance for Industry, 2004). A range of techniques have been employed to monitor hot melt extrusion, with spectroscopic measurements using high temperature probes most widely used (Saerens et al, 2013). Raman and near infra-red (NIR) spectroscopy techniques can provide qualitative and quantitative information about chemical and physical properties (De Beer et al, 2010).…”

Implementation of transmission NIR as a PAT tool for monitoring drug transformation during HME processing

“…The Food and Drug Administration (FDA) introduced the concept of Process Analytical Technologies (PAT) in 2004 for a better fundamental scientific understanding of manufacturing processes in order to ensure the quality of the end product [14,15]. The aim of this initiative is to implement appropriate measurement tools, which can be placed at/in or on-line for monitoring and data analysis via a scientific approach such as chemometrics and Quality by Design (QbD) approach to ensure the production of in-process materials and the final quality of products [16].…”

The effects of polymer carrier, hot melt extrusion process and downstream processing parameters on the moisture sorption properties of amorphous solid dispersions

“…Sensitive and non‐invasive characterization of drug–polymer interactions can be performed quickly, even with the controlled sample temperature and atmosphere. Moreover, FTIR chemical imaging provides straightforward information of miscibility or mixing of the drug and polymer [24,25]. However, the effect of moisture on the drug dispersion homogeneity is still limited by using this visualized technology.…”