Next Article in Journal
Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route
Previous Article in Journal
Evaluation of the Anti-Histoplasma capsulatum Activity of Indole and Nitrofuran Derivatives and Their Pharmacological Safety in Three-Dimensional Cell Cultures
Previous Article in Special Issue
The Value of Bead Coating in the Manufacturing of Amorphous Solid Dispersions: A Comparative Evaluation with Spray Drying
Article

A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development

AbbVie Deutschland GmbH & Co. KG, Global Pharmaceutical R&D, Knollstraße, D-67061 Ludwigshafen am Rhein, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Anne Marie Healy
Pharmaceutics 2022, 14(5), 1044; https://doi.org/10.3390/pharmaceutics14051044
Received: 20 April 2022 / Revised: 7 May 2022 / Accepted: 10 May 2022 / Published: 12 May 2022
Several literature publications have described the potential application of active pharmaceutical ingredient (API)–polymer phase diagrams to identify appropriate temperature ranges for processing amorphous solid dispersion (ASD) formulations via the hot-melt extrusion (HME) technique. However, systematic investigations and reliable applications of the phase diagram as a risk assessment tool for HME are non-existent. Accordingly, within AbbVie, an HME risk classification system (HCS) based on API–polymer phase diagrams has been developed as a material-sparing tool for the early risk assessment of especially high melting temperature APIs, which are typically considered unsuitable for HME. The essence of the HCS is to provide an API risk categorization framework for the development of ASDs via the HME process. The proposed classification system is based on the recognition that the manufacture of crystal-free ASD using the HME process fundamentally depends on the ability of the melt temperature to reach the API’s thermodynamic solubility temperature or above. Furthermore, we explored the API–polymer phase diagram as a simple tool for process design space selection pertaining to API or polymer thermal degradation regions and glass transition temperature-related dissolution kinetics limitations. Application of the HCS was demonstrated via HME experiments with two high melting temperature APIs, sulfamerazine and telmisartan, with the polymers Copovidone and Soluplus. Analysis of the resulting ASDs in terms of the residual crystallinity and degradation showed excellent agreement with the preassigned HCS class. Within AbbVie, the HCS concept has been successfully applied to more than 60 different APIs over the last 8 years as a robust validated risk assessment and quality-by-design (QbD) tool for the development of HME ASDs. View Full-Text
Keywords: amorphous solid dispersion; hot-melt extrusion; HME risk classification system; HME process design space; quality-by-design; telmisartan; sulfamerazine; copovidone; soluplus; APC™ amorphous solid dispersion; hot-melt extrusion; HME risk classification system; HME process design space; quality-by-design; telmisartan; sulfamerazine; copovidone; soluplus; APC™
Show Figures

Graphical abstract

MDPI and ACS Style

Kyeremateng, S.O.; Voges, K.; Dohrn, S.; Sobich, E.; Lander, U.; Weber, S.; Gessner, D.; Evans, R.C.; Degenhardt, M. A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development. Pharmaceutics 2022, 14, 1044. https://doi.org/10.3390/pharmaceutics14051044

AMA Style

Kyeremateng SO, Voges K, Dohrn S, Sobich E, Lander U, Weber S, Gessner D, Evans RC, Degenhardt M. A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development. Pharmaceutics. 2022; 14(5):1044. https://doi.org/10.3390/pharmaceutics14051044

Chicago/Turabian Style

Kyeremateng, Samuel O., Kristin Voges, Stefanie Dohrn, Ekaterina Sobich, Ute Lander, Stefan Weber, David Gessner, Rachel C. Evans, and Matthias Degenhardt. 2022. "A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development" Pharmaceutics 14, no. 5: 1044. https://doi.org/10.3390/pharmaceutics14051044

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop