{"id":"doi:10.1016/j.jconrel.2020.03.026","kind":"article","title":"Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery","authors":["Courtenay AJ","McAlister E","McCrudden MTC","Vora L","Steiner L","Levin G","Levy-Nissenbaum E","Shterman N","Kearney MC","McCarthy HO","Donnelly RF"],"author_count":11,"year":2020,"published":"2020-03-19","venue":"Journal of controlled release : official journal of the Controlled Release Society","cited_by":104,"doi":"10.1016/j.jconrel.2020.03.026","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.jconrel.2020.03.026","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.jconrel.2020.03.026","updated":null,"pmid":"32200001","pmcid":"PMC7262583","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC7262583/pdf","abstract":"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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery\" by Courtenay AJ, McAlister E, McCrudden MTC et al., https://doi.org/10.1016/j.jconrel.2020.03.026, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"psychiatric-therapeutics","name":"Novel Psychiatric Therapeutics","domain_slug":"neuroscience"}],"cited_in_dossiers":[]}