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

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.

Quality of FDM 3D Printed Medicines for Pediatrics: Considerations for Formulation Development, Filament Extrusion, Printing Process and Printer Design

“…Spoerk et al used in-line UV–vis spectroscopy as an analytical tool for characterizing of active ingredients (Estradiol, Estriol, Ibuprofen) and polymer matrices (ethylene vinyl acetate, Eudragit RL-PO). The studies focused on the quantification of the drug for cleaning-in-place strategies [ 58 ]. Wesholowski et al have investigated in-line UV–vis spectroscopy as a PAT tool for preparing solid dispersions of two APIs (carbamazepine and theophylline) with one polymer (copovidone) [ 59 ].…”

“…To avoid changing the complete print head, a system design similar to the design of hot-melt extruders is recommended. Similar to the barrels, the printhead should be demountable and the material touching parts easily accessible [ 58 ]. The coldend of the printhead is placed in the print chamber as well and its cooling fins cannot be cleaned properly.…”