Naratriptan-Loaded Microemulsions for Transdermal Delivery: A Proof-of-Concept Study

Migraine is a neurological disorder characterized by recurrent episodes of intense headache often accompanied by nausea, photophobia, and phonophobia. Although triptans are widely used in the treatment of acute migraine attacks, oral administration may have limitations, including delayed onset of action and gastrointestinal symptoms associated with migraine episodes. In this context, alternative administration strategies have been investigated to improve the systemic delivery of these drugs. This study aimed to develop and conduct preliminary proof-of-concept evaluation of naratriptan-loaded microemulsions as potential systems for transdermal delivery. The formulations (F2N and F4N) were evaluated for physicochemical properties, in vitro release, skin permeation using porcine skin (with and without microneedle pretreatment), stability, and cytotoxicity. The formulations exhibited an average droplet diameter of approximately 18 nm, a polydispersity index below 0.2 and a zeta potential close to neutrality (∼0.32 mV), a result consistent with microemulsion systems whose stability is predominantly governed by thermodynamic equilibrium and interfacial organization. The encapsulation efficiency was 72.5% (F2N) and 73.7% (F4N), with approximately 51% and 48% of naratriptan released over 48 hours, respectively. In the permeation studies, approximately 17% drug permeation was observed in pig skin pretreated with microneedles, indicating that permeation-enhancing strategies such as microneedle pretreatment may contribute to the transdermal transport of naratriptan. These results represent preliminary evidence, and further optimization of the formulation is needed to improve permeation efficiency and more thoroughly evaluate the safety profile of the system.