Development of buspirone hydrochloride-loaded long-acting microneedles for management of anxiety disorders

Buspirone hydrochloride (BSP) is an anxiolytic agent approved for the management of anxiety disorders. The current US-FDA approved medications of BSP are administered via the oral route, which is linked to several disadvantages such as low oral bioavailability and low half-life necessitating multiple daily doses. For chronic diseases such as anxiety disorders, where long-term or lifelong management is often required, these factors impact patient compliance and treatment adherence. The present study offers an alternative treatment approach by investigating the feasibility of sustained transdermal delivery of BSP via long-acting microneedles (MNs). Needle-tip-loaded MNs were fabricated via micro-molding technique using various grades of poly-vinyl alcohol (PVA) namely 4-88, 8-88, 18-88, and 26-88. These MNs were compared using characterization techniques such as Parafilm^® insertion testing, scanning electron microscopy (SEM), confocal microscopy, Fourier transform infrared spectroscopy (FTIR), and histological evaluation of MNs-treated human skin. The effect of different grades of PVA on the structural and mechanical properties of the fabricated MNs was evaluated. Further, in vitro release and permeation tests were conducted to assess the drug release patterns and transdermal delivery across dermatomed human skin over 7-day study periods. The highest release (5507.37 ± 456.88 µg/cm²) and delivery (4705.42 ± 634.57 µg/cm²) were observed from PVA 4-88, with significant differences among the PVA grades based on their properties. Notably, all four types of the fabricated PVA MNs crossed the daily and weekly therapeutic targets for the systemic delivery of BSP. Overall, this study established the feasibility of sustained delivery of BSP across the skin using PVA MNs for the management of anxiety disorders.