Introduction: Migraine is a debilitating neurological disorder characterized by recurrent headaches and sensory disturbances. Current therapies are limited by poor bioavailability and adverse effects, necessitating novel delivery approaches. Nanoemulsions have emerged as promising carriers for lipophilic and hydrophilic drugs, offering improved solubility, stability, and targeted delivery. Methods: A phospholipid-based nanoemulsion was developed to co-deliver Rizatriptan and Cannabidiol for synergistic management of acute migraine. Box-Behnken design was employed to optimize critical formulation variables, including oil concentration, surfactant level, and sonication time. The optimized nanoemulsion was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug release profile, and stability. Ex-vivo permeation studies were also conducted using rat skin to evaluate transdermal delivery potential. Results: The optimized formulation exhibited a mean particle size of less than 200 nm with a narrow PDI, indicating uniform dispersion. Zeta potential values confirmed colloidal stability, while high entrapment efficiencies were achieved for both drugs. In-vitro release studies demonstrated sustained drug release over 24 hours, and ex-vivo permeation confirmed enhanced transdermal flux compared to conventional formulations. The nanoemulsion maintained stability under accelerated conditions, validating its robustness. Discussion: The co-loading of Rizatriptan and Cannabidiol in a phospholipid-based nanoemulsion successfully addressed limitations of conventional dosage forms by improving solubility, stability, and permeation. The synergistic combination offers potential for effective migraine relief with reduced dosing frequency and side effects. Conclusion: The study demonstrates that Rizatriptan–Cannabidiol phospholipid nanoemulsion, optimized using Box-Behnken design, is a promising formulation for enhanced management of acute migraine. Further in-vivo studies are warranted to confirm clinical applicability.
Chauhan et al. (Fri,) studied this question.