title: Process monitoring and visualization solutions for hot-melt extrusion: a review.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Saerens
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
mesh_terms: D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000592:standards*; D004339:Drug Compounding / Q000379:methods* / Q000592:standards; D005615:Freezing; D006358:Hot Temperature; D006801:Humans; D011108:Polymers / Q000737:chemistry; D011786:Quality Control; D012996:Solutions
chemical_list: D004337:Drug Carriers; D011108:Polymers; D012996:Solutions
keywords: hot-melt extrusion; in-process monitoring; process analysis; process understanding