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...
Autores principales: | , , , |
---|---|
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 |