2026-10-11T17:19:53Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32805455 2026-10-01T16:15:59Z portal_1172 item_type_8 month_year_10_2026

Microneedle-mediated delivery of tizanidine for the treatment of spasticity Yilin Cong (20855375) PUREID: 674653834 Tizanidine Spasticity microneedle Long-acting delivery Tizanidine (TZN), a centrally acting α₂-adrenergic agonist used to manage spasticity, is constrained by poor oral bioavailability and a short elimination half-life, necessitating frequent dosing and reducing patient adherence. Transdermal drug delivery via microneedle systems offers a minimally invasive alternative that bypasses the stratum corneum (SC), accesses the dermal microcirculation without pain or specialist administration, and enables controlled input profiles. This work evaluates two complementary microneedle platforms for TZN, dissolving microneedle array patches (MAPs) and hydrogel-forming microneedle array patches (HF-MAPs) and integrates solubility-enhancement strategies to address dissolution-rate limitations. TZN nanocrystals (NCs) were produced by media milling to increase apparent solubility and dissolution rate. The resultant TZN NCs was then incorporated into dissolving MAPs, which exhibited robust needle strength and provided sustained, efficient systemic exposure in in vivo study, consistent with formation of an intradermal drug depot. In parallel, HF MAPs were incorporated with external drug reservoirs designed to deliver TZN without leaving degradable polymers in the skin. Upon insertion, the hydrogel matrix imbibes interstitial fluid, swells, and establishes continuous aqueous conduits between the reservoir and the systemic circulation. Two reservoir formulations, a TZN amorphous solid dispersion and a lyophilised TZN hydrochloride (TZN HCl) patch, were developed and characterised, with evaluation of rehydration, dissolution behaviour, and physicochemical stability to define feasible long-acting release profiles. The in vivo pharmacokinetic profile of HF-MAPs combined with TZN HCl lyophilised reservoirs was subsequently investigated. Collectively, these findings indicated that NC-loaded dissolving MAPs can enhance intradermal deposition and systemic availability of TZN, while HF-MAPs combined with lyophilised reservoirs provide a potential practical strategy for sustained transdermal administration. Microneedle technology offers a translational pathway to improve TZN pharmacokinetics, reduce dosing frequency, and ultimately support better patient adherence. Beyond spasticity management, the platform is generalisable to poorly soluble drugs and can inform the design of future long-acting transdermal therapies. <br><br><i>Thesis is embargoed until 31 July 2031.</i> 2026-10-01T16:15:59Z Text Thesis 10.17034/32805455.v1 https://figshare.com/articles/thesis/Microneedle-mediated_delivery_of_tizanidine_for_the_treatment_of_spasticity/32805455 All Rights Reserved Open Access after 2031-07-31