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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...

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Autores principales: Guner, Gulenay, Amjad, Ayesha, Berrios, Matthew, Kannan, Manisha, Bilgili, Ecevit
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
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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.
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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
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