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A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development
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, syste...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147278/ https://www.ncbi.nlm.nih.gov/pubmed/35631630 http://dx.doi.org/10.3390/pharmaceutics14051044 |
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author | Kyeremateng, Samuel O. Voges, Kristin Dohrn, Stefanie Sobich, Ekaterina Lander, Ute Weber, Stefan Gessner, David Evans, Rachel C. Degenhardt, Matthias |
author_facet | Kyeremateng, Samuel O. Voges, Kristin Dohrn, Stefanie Sobich, Ekaterina Lander, Ute Weber, Stefan Gessner, David Evans, Rachel C. Degenhardt, Matthias |
author_sort | Kyeremateng, Samuel O. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9147278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91472782022-05-29 A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development Kyeremateng, Samuel O. Voges, Kristin Dohrn, Stefanie Sobich, Ekaterina Lander, Ute Weber, Stefan Gessner, David Evans, Rachel C. Degenhardt, Matthias Pharmaceutics Article 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. MDPI 2022-05-12 /pmc/articles/PMC9147278/ /pubmed/35631630 http://dx.doi.org/10.3390/pharmaceutics14051044 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kyeremateng, Samuel O. Voges, Kristin Dohrn, Stefanie Sobich, Ekaterina Lander, Ute Weber, Stefan Gessner, David Evans, Rachel C. Degenhardt, Matthias A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title | A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title_full | A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title_fullStr | A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title_full_unstemmed | A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title_short | A Hot-Melt Extrusion Risk Assessment Classification System for Amorphous Solid Dispersion Formulation Development |
title_sort | hot-melt extrusion risk assessment classification system for amorphous solid dispersion formulation development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9147278/ https://www.ncbi.nlm.nih.gov/pubmed/35631630 http://dx.doi.org/10.3390/pharmaceutics14051044 |
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