Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion

Martin Spoerk*, Ioannis Koutsamanis, Josip Matic, Simone Eder, Carolina Patricia Alva Zuniga, Johannes Poms, Jesus Alberto Afonso Urich, Raymar Andreina Lara Garcia, Klaus Nickisch, Karin Eggenreich, Andreas Berghaus, Kathrin Reusch, Yorick Relle, Johannes Khinast, Amrit Paudel*

*Corresponding author for this work

Research output: Other contribution

Abstract

To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug. First, an in-line quantification by means of UV–Vis spectroscopy was successfully implemented to assess very low active pharmaceutical ingredient (API) concentrations in the extrudates during a cleaning procedure for the first time. Secondly, a novel in-situ solvent-based cleaning approach was developed and its usability was evaluated and compared to a polymer-based cleaning sequence. Comparing the in-line data to typical swab and rinse tests of the process equipment indicated that inaccessible parts of the equipment were still contaminated after the polymer-based cleaning procedure, although no API was detected in the extrudate. Nevertheless, the novel solvent-based cleaning approach proved to be suitable for removing API residue from the majority of problematic equipment parts and can potentially enable a full API cleaning-in-place of a pharmaceutical extruder for the first time.

Original languageEnglish
Number of pages21
Edition6
Volume12
DOIs
Publication statusPublished - Jun 2020

Publication series

NamePharmaceutics

Keywords

  • cleaning verification
  • cleaning-in-place
  • hot melt extrusion
  • API contamination
  • UV-Vis spectroscopy
  • process analytical technology
  • swab and rinse tests
  • estradiol
  • estriol
  • ibuprofen
  • Hot melt extrusion
  • Cleaning verification
  • Estradiol
  • Process analytical technology
  • Ibuprofen
  • Swab and rinse tests
  • Cleaning-in-place
  • Estriol
  • UV–Vis spectroscopy

ASJC Scopus subject areas

  • Pharmaceutical Science

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