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Article

Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes

Department of Pharmaceutics, Pharmaceutical Institute, University of Bonn, 53121 Bonn, Germany
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Author to whom correspondence should be addressed.
Pharmaceutics 2023, 15(3), 723; https://doi.org/10.3390/pharmaceutics15030723
Submission received: 25 January 2023 / Revised: 14 February 2023 / Accepted: 20 February 2023 / Published: 22 February 2023
(This article belongs to the Special Issue Developing Peptide and Protein Drug Formulations)

Abstract

Hot-melt extrusion (HME) is used for the production of solid protein formulations mainly for two reasons: increased protein stability in solid state and/or long-term release systems (e.g., protein-loaded implants). However, HME requires considerable amounts of material even at small-scale (>2 g batch size). In this study, we introduced vacuum compression molding (VCM) as a predictive screening tool of protein stability for potential HME processing. The focus was to identify appropriate polymeric matrices prior to extrusion and evaluation of protein stability after thermal stress using only a few milligrams of protein. The protein stability of lysozyme, BSA, and human insulin embedded in PEG 20,000, PLGA, or EVA by VCM was investigated by DSC, FT-IR, and SEC. The results from the protein-loaded discs provided important insights into the solid-state stabilizing mechanisms of protein candidates. We demonstrated the successful application of VCM for a set of proteins and polymers, showing, in particular, a high potential for EVA as a polymeric matrix for solid-state stabilization of proteins and the production of extended-release dosage forms. Stable protein-polymer mixtures with sufficient protein stability after VCM could be then introduced to a combination of thermal and shear stress by HME and further investigated with regard to their process-related protein stability.
Keywords: vacuum compression molding; screening tool; formulation development; protein stability; protein characterization; biopharmaceuticals; solid-state stability vacuum compression molding; screening tool; formulation development; protein stability; protein characterization; biopharmaceuticals; solid-state stability
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MDPI and ACS Style

Dauer, K.; Wagner, K.G. Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes. Pharmaceutics 2023, 15, 723. https://doi.org/10.3390/pharmaceutics15030723

AMA Style

Dauer K, Wagner KG. Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes. Pharmaceutics. 2023; 15(3):723. https://doi.org/10.3390/pharmaceutics15030723

Chicago/Turabian Style

Dauer, Katharina, and Karl G. Wagner. 2023. "Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes" Pharmaceutics 15, no. 3: 723. https://doi.org/10.3390/pharmaceutics15030723

APA Style

Dauer, K., & Wagner, K. G. (2023). Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes. Pharmaceutics, 15(3), 723. https://doi.org/10.3390/pharmaceutics15030723

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