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Pharmaceutics
Volume 12
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10.3390/pharmaceutics12020116
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Article

Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy

by
Lærke Arnfast
1,†,
Jeroen van Renterghem
2,
Johanna Aho
1,‡,
Johan Bøtker
1,
Dhara Raijada
1,§,
Stefania Baldursdóttir
1,‖,
Thomas De Beer
2 and
Jukka Rantanen
1,*
1
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
2
Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium
*
Author to whom correspondence should be addressed.
†
Current address: Eurofins Amatsigroup, Industriepark Zwijnaarde 7, B-9000 Ghent, Belgium.
‡
Current address: Novo Nordisk A/S, Brennum Park, 3400 Hillerød, Denmark.
§
Current address: Pharmaceutical R & D, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
‖
Current address: Lilja Skincare, Les Bourdas, 65560 Ferrières, France.
Pharmaceutics 2020, 12(2), 116; https://doi.org/10.3390/pharmaceutics12020116
Submission received: 8 November 2019 / Revised: 16 January 2020 / Accepted: 17 January 2020 / Published: 1 February 2020
(This article belongs to the Special Issue Hot-Melt Extrusion)
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Abstract

The specific aim in this study was to understand the effect of critical process parameters on the solid form composition of model drug compounds during hot melt extrusion using in-line Raman spectroscopy combined with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) modeling for semi-quantitative kinetic profiling. It was observed that the hydrate and anhydrate solid forms of two model drugs in the melts of nitrofurantoin (NF):polyethylene oxide (PEO) and piroxicam (PRX):PEO could be resolved from a MCR-ALS model without an external calibration dataset. Based on this model, the influence of two critical process parameters (shear and temperature) on the solid form composition could be evaluated in a real-time mode and the kinetics of complex transformation pathways could be explored. Additionally, the dehydration pathways of NF monohydrate and PRX monohydrate in molten PEO could be derived. It can be concluded that dehydration of both hydrates in PEO occurs via competing mechanisms—a solution-mediated transformation pathway and a solid–solid transformation, and that the balance between these mechanisms is determined by the combined effect of both temperature and shear. Another important observation was that the water released from these hydrate compounds has a detectable effect on the rheological characteristics of this mixture.
Keywords: dehydration; hydrates/solvates; kinetics; Raman spectroscopy; extrusion; processing; preformulation; solid state stability; transformation dehydration; hydrates/solvates; kinetics; Raman spectroscopy; extrusion; processing; preformulation; solid state stability; transformation

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MDPI and ACS Style

Arnfast, L.; van Renterghem, J.; Aho, J.; Bøtker, J.; Raijada, D.; Baldursdóttir, S.; De Beer, T.; Rantanen, J. Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy. Pharmaceutics 2020, 12, 116. https://doi.org/10.3390/pharmaceutics12020116

AMA Style

Arnfast L, van Renterghem J, Aho J, Bøtker J, Raijada D, Baldursdóttir S, De Beer T, Rantanen J. Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy. Pharmaceutics. 2020; 12(2):116. https://doi.org/10.3390/pharmaceutics12020116

Chicago/Turabian Style

Arnfast, Lærke, Jeroen van Renterghem, Johanna Aho, Johan Bøtker, Dhara Raijada, Stefania Baldursdóttir, Thomas De Beer, and Jukka Rantanen. 2020. "Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy" Pharmaceutics 12, no. 2: 116. https://doi.org/10.3390/pharmaceutics12020116

APA Style

Arnfast, L., van Renterghem, J., Aho, J., Bøtker, J., Raijada, D., Baldursdóttir, S., De Beer, T., & Rantanen, J. (2020). Exploring the Complexity of Processing-Induced Dehydration during Hot Melt Extrusion Using In-Line Raman Spectroscopy. Pharmaceutics, 12(2), 116. https://doi.org/10.3390/pharmaceutics12020116

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