Cargando…
Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions
The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the s...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964794/ https://www.ncbi.nlm.nih.gov/pubmed/36839772 http://dx.doi.org/10.3390/pharmaceutics15020450 |
_version_ | 1784896596736999424 |
---|---|
author | Guner, Gulenay Amjad, Ayesha Berrios, Matthew Kannan, Manisha Bilgili, Ecevit |
author_facet | Guner, Gulenay Amjad, Ayesha Berrios, Matthew Kannan, Manisha Bilgili, Ecevit |
author_sort | Guner, Gulenay |
collection | PubMed |
description | The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the solution-mediated precipitation from griseofulvin ASDs. Nanoparticle crystals (nanoseeds) were used as a more realistic surrogate for residual crystals compared with conventional micron-sized seeds. ASDs of griseofulvin with Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC) were prepared by spray-drying. Nanoseeds produced by wet media milling were used in the dissolution and desupersaturation experiments. DLS, SEM, XRPD, and DSC were used for characterization. The results from the solvent-shift tests suggest that the drug nanoseeds led to a faster and higher extent of desupersaturation than the as-received micron-sized crystals and that the higher seed loading facilitated desupersaturation. Sol was the only effective nucleation inhibitor; the overall precipitation inhibition capability was ranked: Sol > HPMC > VA64. In the dissolution tests, only the Sol-based ASDs generated significant supersaturation, which decreased upon an increase in the nanoseed loading. This study has demonstrated the importance of using drug nanocrystals in lieu of conventional coarse crystals in desupersaturation and dissolution tests in ASD development. |
format | Online Article Text |
id | pubmed-9964794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99647942023-02-26 Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions Guner, Gulenay Amjad, Ayesha Berrios, Matthew Kannan, Manisha Bilgili, Ecevit Pharmaceutics Article The impact of residual drug crystals that are formed during the production and storage of amorphous solid dispersions (ASDs) has been studied using micron-sized seed crystals in solvent-shift (desupersaturation) and dissolution tests. This study examines the impacts of the seed size loading on the solution-mediated precipitation from griseofulvin ASDs. Nanoparticle crystals (nanoseeds) were used as a more realistic surrogate for residual crystals compared with conventional micron-sized seeds. ASDs of griseofulvin with Soluplus (Sol), Kollidon VA64 (VA64), and hydroxypropyl methyl cellulose (HPMC) were prepared by spray-drying. Nanoseeds produced by wet media milling were used in the dissolution and desupersaturation experiments. DLS, SEM, XRPD, and DSC were used for characterization. The results from the solvent-shift tests suggest that the drug nanoseeds led to a faster and higher extent of desupersaturation than the as-received micron-sized crystals and that the higher seed loading facilitated desupersaturation. Sol was the only effective nucleation inhibitor; the overall precipitation inhibition capability was ranked: Sol > HPMC > VA64. In the dissolution tests, only the Sol-based ASDs generated significant supersaturation, which decreased upon an increase in the nanoseed loading. This study has demonstrated the importance of using drug nanocrystals in lieu of conventional coarse crystals in desupersaturation and dissolution tests in ASD development. MDPI 2023-01-30 /pmc/articles/PMC9964794/ /pubmed/36839772 http://dx.doi.org/10.3390/pharmaceutics15020450 Text en © 2023 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 Guner, Gulenay Amjad, Ayesha Berrios, Matthew Kannan, Manisha Bilgili, Ecevit Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title | Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title_full | Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title_fullStr | Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title_full_unstemmed | Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title_short | Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions |
title_sort | nanoseeded desupersaturation and dissolution tests for elucidating supersaturation maintenance in amorphous solid dispersions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964794/ https://www.ncbi.nlm.nih.gov/pubmed/36839772 http://dx.doi.org/10.3390/pharmaceutics15020450 |
work_keys_str_mv | AT gunergulenay nanoseededdesupersaturationanddissolutiontestsforelucidatingsupersaturationmaintenanceinamorphoussoliddispersions AT amjadayesha nanoseededdesupersaturationanddissolutiontestsforelucidatingsupersaturationmaintenanceinamorphoussoliddispersions AT berriosmatthew nanoseededdesupersaturationanddissolutiontestsforelucidatingsupersaturationmaintenanceinamorphoussoliddispersions AT kannanmanisha nanoseededdesupersaturationanddissolutiontestsforelucidatingsupersaturationmaintenanceinamorphoussoliddispersions AT bilgiliecevit nanoseededdesupersaturationanddissolutiontestsforelucidatingsupersaturationmaintenanceinamorphoussoliddispersions |