Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy.

Jeroen Van Renterghem, Ashish Kumar, Chris Vervaet, Jean Paul Remon, Ingmar Nopens, Yvan Vander Heyden, Thomas De Beer

International journal of pharmaceutics 2017 Jan 30

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Mixing of raw materials (drug+polymer) in the investigated mini pharma melt extruder is achieved by using co-rotating conical twin screws and an internal recirculation channel. In-line Raman spectroscopy was implemented in the barrels, allowing monitoring of the melt during processing. The aim of this study was twofold: to investigate (I) the influence of key process parameters (screw speed - barrel temperature) upon the product solid-state transformation during processing of a sustained release formulation in recirculation mode; (II) the influence of process parameters (screw speed - barrel temperature - recirculation time) upon mixing of a crystalline drug (tracer) in an amorphous polymer carrier by means of residence time distribution (RTD) measurements. The results indicated a faster mixing endpoint with increasing screw speed. Processing a high drug load formulation above the drug melting temperature resulted in the production of amorphous drug whereas processing below the drug melting point produced solid dispersions with partially amorphous/crystalline drug. Furthermore, increasing the screw speed resulted in lower drug crystallinity of the solid dispersion. RTD measurements elucidated the improved mixing capacity when using the recirculation channel. In-line Raman spectroscopy has shown to be an adequate PAT-tool for product solid-state monitoring and elucidation of the mixing behavior during processing in a mini extruder. Copyright © 2016 Elsevier B.V. All rights reserved.

Citation

Jeroen Van Renterghem, Ashish Kumar, Chris Vervaet, Jean Paul Remon, Ingmar Nopens, Yvan Vander Heyden, Thomas De Beer. Elucidation and visualization of solid-state transformation and mixing in a pharmaceutical mini hot melt extrusion process using in-line Raman spectroscopy. International journal of pharmaceutics. 2017 Jan 30;517(1-2):119-127