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Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery

Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and adva...

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Autores principales: Courtenay, Aaron J., McAlister, Emma, McCrudden, Maelíosa T.C., Vora, Lalit, Steiner, Lilach, Levin, Galit, Levy-Nissenbaum, Etgar, Shterman, Nava, Kearney, Mary-Carmel, McCarthy, Helen O., Donnelly, Ryan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Publishers 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262583/
https://www.ncbi.nlm.nih.gov/pubmed/32200001
http://dx.doi.org/10.1016/j.jconrel.2020.03.026
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author Courtenay, Aaron J.
McAlister, Emma
McCrudden, Maelíosa T.C.
Vora, Lalit
Steiner, Lilach
Levin, Galit
Levy-Nissenbaum, Etgar
Shterman, Nava
Kearney, Mary-Carmel
McCarthy, Helen O.
Donnelly, Ryan F.
author_facet Courtenay, Aaron J.
McAlister, Emma
McCrudden, Maelíosa T.C.
Vora, Lalit
Steiner, Lilach
Levin, Galit
Levy-Nissenbaum, Etgar
Shterman, Nava
Kearney, Mary-Carmel
McCarthy, Helen O.
Donnelly, Ryan F.
author_sort Courtenay, Aaron J.
collection PubMed
description Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and advanced delivery platforms could provide an alternative parenteral route of esketamine dosing in patients. Hydrogel-forming microneedle arrays facilitate transdermal delivery of drugs by penetrating the outer layer of the skins surface, absorbing interstitial skin fluid and swelling. This subsequently facilitates permeation of medicines into the dermal microcirculation. This paper outlines the in vitro formulation development for hydrogel-forming microneedle arrays containing esketamine. Analytical methods for the detection and quantitation of esketamine were developed and validated according to International Conference on Harmonisation standards. Hydrogel-forming microneedle arrays were fully characterised for their mechanical strength and skin insertion properties. Furthermore, a series of esketamine containing polymeric films and lyophilised reservoirs were assessed as drug reservoir candidates. Dissolution testing and content drug recovery was carried out, followed by permeation studies using 350 μm thick neonatal porcine skin in modified Franz cell apparatus. Lead reservoir candidates were selected based on measured physicochemical properties and brought forward for testing in female Sprague-Dawley rats. Plasma samples were analysed using reverse phase high performance liquid chromatography for esketamine. Both polymeric film and lyophilised reservoirs candidate patches achieved esketamine plasma concentrations higher than the target concentration of 0.15–0.3 μg/ml over 24 h. Mean plasma concentrations in rats, 24 h post-application of microneedle patches with drug reservoir F3 and LW3, were 0.260 μg/ml and 0.498 μg/ml, respectively. This developmental study highlights the potential success of hydrogel-forming microneedle arrays as a transdermal drug delivery platform for ESK and supports moving to in vivo tests in a larger animal model.
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spelling pubmed-72625832020-06-10 Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery Courtenay, Aaron J. McAlister, Emma McCrudden, Maelíosa T.C. Vora, Lalit Steiner, Lilach Levin, Galit Levy-Nissenbaum, Etgar Shterman, Nava Kearney, Mary-Carmel McCarthy, Helen O. Donnelly, Ryan F. J Control Release Article Treatment resistant depression is, by definition, difficult to treat using standard therapeutic interventions. Recently, esketamine has been shown as a viable rescue treatment option in patients in depressive crisis states. However, IV administration is associated with a number of drawbacks and advanced delivery platforms could provide an alternative parenteral route of esketamine dosing in patients. Hydrogel-forming microneedle arrays facilitate transdermal delivery of drugs by penetrating the outer layer of the skins surface, absorbing interstitial skin fluid and swelling. This subsequently facilitates permeation of medicines into the dermal microcirculation. This paper outlines the in vitro formulation development for hydrogel-forming microneedle arrays containing esketamine. Analytical methods for the detection and quantitation of esketamine were developed and validated according to International Conference on Harmonisation standards. Hydrogel-forming microneedle arrays were fully characterised for their mechanical strength and skin insertion properties. Furthermore, a series of esketamine containing polymeric films and lyophilised reservoirs were assessed as drug reservoir candidates. Dissolution testing and content drug recovery was carried out, followed by permeation studies using 350 μm thick neonatal porcine skin in modified Franz cell apparatus. Lead reservoir candidates were selected based on measured physicochemical properties and brought forward for testing in female Sprague-Dawley rats. Plasma samples were analysed using reverse phase high performance liquid chromatography for esketamine. Both polymeric film and lyophilised reservoirs candidate patches achieved esketamine plasma concentrations higher than the target concentration of 0.15–0.3 μg/ml over 24 h. Mean plasma concentrations in rats, 24 h post-application of microneedle patches with drug reservoir F3 and LW3, were 0.260 μg/ml and 0.498 μg/ml, respectively. This developmental study highlights the potential success of hydrogel-forming microneedle arrays as a transdermal drug delivery platform for ESK and supports moving to in vivo tests in a larger animal model. Elsevier Science Publishers 2020-06-10 /pmc/articles/PMC7262583/ /pubmed/32200001 http://dx.doi.org/10.1016/j.jconrel.2020.03.026 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Courtenay, Aaron J.
McAlister, Emma
McCrudden, Maelíosa T.C.
Vora, Lalit
Steiner, Lilach
Levin, Galit
Levy-Nissenbaum, Etgar
Shterman, Nava
Kearney, Mary-Carmel
McCarthy, Helen O.
Donnelly, Ryan F.
Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title_full Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title_fullStr Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title_full_unstemmed Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title_short Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
title_sort hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262583/
https://www.ncbi.nlm.nih.gov/pubmed/32200001
http://dx.doi.org/10.1016/j.jconrel.2020.03.026
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