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High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach
Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeati...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572106/ https://www.ncbi.nlm.nih.gov/pubmed/31083433 http://dx.doi.org/10.3390/pharmaceutics11050227 |
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author | Jacobsen, Ann-Christin Krupa, Anna Brandl, Martin Bauer-Brandl, Annette |
author_facet | Jacobsen, Ann-Christin Krupa, Anna Brandl, Martin Bauer-Brandl, Annette |
author_sort | Jacobsen, Ann-Christin |
collection | PubMed |
description | Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeation employing a two-compartment 96-well plate. Freeze-drying from hydro-alcoholic solutions was used to prepare amorphous formulations. The screening approach was tested on amorphous and crystalline tadalafil formulations with and without Soluplus(®). The workflow consisted of: (1) dispersion of the formulations; (2) incubation within the two-compartment plate, where a dialysis membrane separated donor (dispersed formulation) and acceptor; (3) sampling (donor and acceptor), where donor samples were centrifuged to remove non-dissolved material; and (4) quantification by UHPLC-UV. To identify optimal screening conditions, the following parameters were varied: dispersion medium (buffer/biomimetic media), acceptor medium (buffer/surfactant solutions), and incubation time (1, 3, and 6 h). Surfactants (acceptor) increased tadalafil permeation. Biomimetic medium (donor) enhanced dissolution, but not permeation, except for freeze-dried tadalafil, for which the permeated amount increased. The predictiveness was evaluated by comparing dissolution-/permeation-results with in vivo bioavailability. In general, both dissolution and permeation reflected bioavailability, whereof the latter was a better predictor. High-throughput dissolution/permeation is regarded promising for formulation screening. |
format | Online Article Text |
id | pubmed-6572106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65721062019-06-18 High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach Jacobsen, Ann-Christin Krupa, Anna Brandl, Martin Bauer-Brandl, Annette Pharmaceutics Article Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeation employing a two-compartment 96-well plate. Freeze-drying from hydro-alcoholic solutions was used to prepare amorphous formulations. The screening approach was tested on amorphous and crystalline tadalafil formulations with and without Soluplus(®). The workflow consisted of: (1) dispersion of the formulations; (2) incubation within the two-compartment plate, where a dialysis membrane separated donor (dispersed formulation) and acceptor; (3) sampling (donor and acceptor), where donor samples were centrifuged to remove non-dissolved material; and (4) quantification by UHPLC-UV. To identify optimal screening conditions, the following parameters were varied: dispersion medium (buffer/biomimetic media), acceptor medium (buffer/surfactant solutions), and incubation time (1, 3, and 6 h). Surfactants (acceptor) increased tadalafil permeation. Biomimetic medium (donor) enhanced dissolution, but not permeation, except for freeze-dried tadalafil, for which the permeated amount increased. The predictiveness was evaluated by comparing dissolution-/permeation-results with in vivo bioavailability. In general, both dissolution and permeation reflected bioavailability, whereof the latter was a better predictor. High-throughput dissolution/permeation is regarded promising for formulation screening. MDPI 2019-05-10 /pmc/articles/PMC6572106/ /pubmed/31083433 http://dx.doi.org/10.3390/pharmaceutics11050227 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jacobsen, Ann-Christin Krupa, Anna Brandl, Martin Bauer-Brandl, Annette High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title | High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title_full | High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title_fullStr | High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title_full_unstemmed | High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title_short | High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach |
title_sort | high-throughput dissolution/permeation screening—a 96-well two-compartment microplate approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572106/ https://www.ncbi.nlm.nih.gov/pubmed/31083433 http://dx.doi.org/10.3390/pharmaceutics11050227 |
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