Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kyeremateng, Samuel O., Voges, Kristin, Dohrn, Stefanie, Sobich, Ekaterina, Lander, Ute, Weber, Stefan, Gessner, David, Evans, Rachel C., Degenhardt, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784716768296566784
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
work_keys_str_mv AT kyerematengsamuelo ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT vogeskristin ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT dohrnstefanie ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT sobichekaterina ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT landerute ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT weberstefan ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT gessnerdavid ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT evansrachelc ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT degenhardtmatthias ahotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT kyerematengsamuelo hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT vogeskristin hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT dohrnstefanie hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT sobichekaterina hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT landerute hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT weberstefan hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT gessnerdavid hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT evansrachelc hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment
AT degenhardtmatthias hotmeltextrusionriskassessmentclassificationsystemforamorphoussoliddispersionformulationdevelopment