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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...

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Autores principales: Jacobsen, Ann-Christin, Krupa, Anna, Brandl, Martin, Bauer-Brandl, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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