Transdermal Delivery of Zaleplon Through Dissolving-Swellable Microneedles: An in Vitro/ in Vivo Study in Rats With Insomnia Induced by Para-Chlorophenylalanine Publisher



Ghaedi M ; Varshosaz J ; Rabbani M ; Mohammadsharifi Renani A
Source: Journal of Drug Delivery Science and Technology Published:2026

Abstract

Microneedles represent a type of formulation utilized for the transference of materials through the skin. The rate at which substances are transferred into the body can be controlled in comparison to oral and parenteral methods, thereby potentially reducing side effects. The aim of this study was to develop dissolving microneedle patches (MNPs) from zaleplon, a non-benzodiazepine sleep inducer. Zaleplon exhibits low solubility in water and possesses a 30 % oral bioavailability due to considerable first-pass metabolism; thus, enhancing its solubility is crucial for more effective and rapid delivery via microneedles. As a result, a solvent exchange method utilizing a 5:1 ratio of polyvinyl alcohol (PVA) to drug was employed to formulate a dispersion of zaleplon within a hydrophilic polymer. This was subsequently followed by freeze-drying to obtain a solid dispersion of the drug. After characterizing the solid dispersions of zaleplon through measurements of saturated solubility, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), the material was utilized to fabricate dissolving microneedles using a micro-molding approach. Various ratios of polyvinyl pyrrolidone (PVP), PVA, and hydroxypropyl methylcellulose (HPMC) were employed as the base for the microneedles, and the resulting microneedles were evaluated for their zaleplon content, release from MNPs, mechanical properties, skin penetration capability, hydrophilicity, structural stability, swell-ability and in vitro deformation. Then the effects of oral zaleplon and MNPs were assessed regarding sleep duration and onset in rats with para-chlorophenylalanine-induced insomnia. The solid dispersion of zaleplon enhanced its water solubility by 6 times (242.03 ± 16.99 μg/mL vs . 40 μg/mL). The optimal formulation comprised 40 wt% PVA, 40 wt% PVP, and 20 wt% HPMC, which facilitated easy penetration into the skin and released over 70 % of zaleplon within 60 min. In vivo results demonstrated that zaleplon microneedles had a faster onset of action (approximately 7.5 min quicker) and extended the duration of sleep more than twice as long as the oral group (100 min compared to 40 min). It can be concluded that zaleplon MNP might be more effective than the oral administration method in managing insomnia. Copyright © 2026. Published by Elsevier B.V.