Cargando…

Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying

Presently, a large number of drug molecules in development are BCS class II or IV compounds with poor aqueous solubility. Various novel solubilization techniques have been used to enhance drug solubility. Among them, amorphous solid dispersions (ASD), which convert a crystalline drug into an amorpho...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yongjun, Mann, Amanda K. P., Zhang, Dan, Yang, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401923/
https://www.ncbi.nlm.nih.gov/pubmed/34452269
http://dx.doi.org/10.3390/pharmaceutics13081307
_version_ 1783745665707278336
author Li, Yongjun
Mann, Amanda K. P.
Zhang, Dan
Yang, Zhen
author_facet Li, Yongjun
Mann, Amanda K. P.
Zhang, Dan
Yang, Zhen
author_sort Li, Yongjun
collection PubMed
description Presently, a large number of drug molecules in development are BCS class II or IV compounds with poor aqueous solubility. Various novel solubilization techniques have been used to enhance drug solubility. Among them, amorphous solid dispersions (ASD), which convert a crystalline drug into an amorphous mixture of drug and polymer, have been demonstrated to be an effective tool in enhancing drug solubility and bioavailability. There are multiple ways to produce amorphous solid dispersions. The goal of the present study is to investigate two commonly used processing methods, hot-melt extrusion (HME) and spray drying, and their impact on drug bioperformance. The amorphous solid dispersions of a model compound, posaconazole (25% drug loading) in HPMCAS-MF, were successfully manufactured via the two processing routes, and the physicochemical properties, in vitro and in vivo performance of the resulting ASDs were characterized and compared. It was found that in vitro drug release of the ASDs from two-stage dissolution was significantly different. However, the two ASDs showed similar in vivo performance based on cynomolgus monkey PK studies. A mechanistic understanding of the in vitro and in vivo behaviors of the solid dispersions was discussed.
format Online
Article
Text
id pubmed-8401923
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84019232021-08-29 Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying Li, Yongjun Mann, Amanda K. P. Zhang, Dan Yang, Zhen Pharmaceutics Article Presently, a large number of drug molecules in development are BCS class II or IV compounds with poor aqueous solubility. Various novel solubilization techniques have been used to enhance drug solubility. Among them, amorphous solid dispersions (ASD), which convert a crystalline drug into an amorphous mixture of drug and polymer, have been demonstrated to be an effective tool in enhancing drug solubility and bioavailability. There are multiple ways to produce amorphous solid dispersions. The goal of the present study is to investigate two commonly used processing methods, hot-melt extrusion (HME) and spray drying, and their impact on drug bioperformance. The amorphous solid dispersions of a model compound, posaconazole (25% drug loading) in HPMCAS-MF, were successfully manufactured via the two processing routes, and the physicochemical properties, in vitro and in vivo performance of the resulting ASDs were characterized and compared. It was found that in vitro drug release of the ASDs from two-stage dissolution was significantly different. However, the two ASDs showed similar in vivo performance based on cynomolgus monkey PK studies. A mechanistic understanding of the in vitro and in vivo behaviors of the solid dispersions was discussed. MDPI 2021-08-21 /pmc/articles/PMC8401923/ /pubmed/34452269 http://dx.doi.org/10.3390/pharmaceutics13081307 Text en © 2021 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
Li, Yongjun
Mann, Amanda K. P.
Zhang, Dan
Yang, Zhen
Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title_full Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title_fullStr Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title_full_unstemmed Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title_short Processing Impact on In Vitro and In Vivo Performance of Solid Dispersions—A Comparison between Hot-Melt Extrusion and Spray Drying
title_sort processing impact on in vitro and in vivo performance of solid dispersions—a comparison between hot-melt extrusion and spray drying
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401923/
https://www.ncbi.nlm.nih.gov/pubmed/34452269
http://dx.doi.org/10.3390/pharmaceutics13081307
work_keys_str_mv AT liyongjun processingimpactoninvitroandinvivoperformanceofsoliddispersionsacomparisonbetweenhotmeltextrusionandspraydrying
AT mannamandakp processingimpactoninvitroandinvivoperformanceofsoliddispersionsacomparisonbetweenhotmeltextrusionandspraydrying
AT zhangdan processingimpactoninvitroandinvivoperformanceofsoliddispersionsacomparisonbetweenhotmeltextrusionandspraydrying
AT yangzhen processingimpactoninvitroandinvivoperformanceofsoliddispersionsacomparisonbetweenhotmeltextrusionandspraydrying