Design and formulation of fast-dissolving microneedles for the rapid transdermal delivery of lorazepam

This study investigates lorazepam-loaded dissolving microneedles (LMNs) as a fast-acting and minimally invasive treatment for status epilepticus. The LMNs were developed using a micro-moulding technique with an optimised combination of PVP K30, Dextran 40 and Pullulan. Their stability was confirmed through Fourier transform infra-red (FTIR) spectroscopy and X-ray diffraction (XRD) analysis. The Parafilm^® membrane insertion test demonstrated 100% penetration efficiency, verifying their ability to effectively pierce the skin. Scanning electron microscopy (SEM) imaging revealed well-defined microneedles with precise dimensions (800 µm height, 200 µm base and 500 µm pitch). The LMNs rapidly dissolved in the subdermal layer of porcine skin. An <i>ex vivo</i> drug diffusion study showed that 3-5% of the encapsulated lorazepam was released within 30 min, with a cumulative release of 79.3% over 24 h. An acute dermal irritation study confirmed the biocompatibility and skin tolerance of the LMNs. Additionally, an <i>in vivo</i> anti-convulsant efficacy study in Albino Wistar rats subjected to maximal electroshock seizures demonstrated significant anticonvulsant effects (<i>p</i> < .05), confirming efficient systemic delivery of lorazepam. These findings highlight LMNs as a rapid-acting, non-invasive transdermal drug delivery system for managing status epilepticus, particularly in ambulatory care settings.