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<p>Migraine is a highly disabling neurological disorder that significantly affects patients’ productivity and quality of life. Zolmitriptan, a selective serotonin receptor agonist, is widely prescribed for acute migraine relief. However, it suffers from limited oral bioavailability due to hepatic first-pass metabolism, rapid clearance, and delayed onset of action, particularly during migraine-associated gastrointestinal disturbances. These limitations have led to the development of new delivery strategies to improve zolmitriptan’s effectiveness and patient outcomes. This review provides a comprehensive analysis of zolmitriptan delivery systems, classified into two developmental phases. Phase I approaches focused on conventional transmucosal and transdermal systems, such as fast-dissolving oral films, sublingual tablets, buccal films, and adhesive patches, which successfully bypass first-pass metabolism and improve the onset of action. However, these delivery systems remain constrained by variable permeability and inconsistent absorption. Phase II strategies focus on nanotechnology-based formulations, including polymeric nanoparticles, solid lipid nanoparticles, bilosomes, novasomes, spanlastics, transferosomes, niosomes, terpesomes, nanostructured lipid carriers, and nanolipomers. These platforms demonstrated superior brain-targeting potential, prolonged pharmacological effects, and higher bioavailability compared to traditional formulations. Special emphasis is placed on non-invasive routes such as intranasal, buccal, and transdermal administration, which offer rapid migraine relief, sustained efficacy, and improved patient adherence. Stepwise innovation in zolmitriptan delivery has progressed from conventional dosage forms to advanced nanocarriers that enhance bioavailability, brain targeting, and clinical efficacy. Future research should focus on patient-tailored delivery strategies, smart responsive carriers, and drug combinations that lower recurrence and improve long-term results. These advances can make migraine treatment more effective and practical.</p>

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Transforming Zolmitriptan Delivery: A Comprehensive Review of Strategies, Challenges, and Future Perspectives

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Mai Magdy Eltaweel,
  • Diana Edwar Aziz,
  • Alaa Emad Eldeeb,
  • Mai Ahmed Tawfik

摘要

Migraine is a highly disabling neurological disorder that significantly affects patients’ productivity and quality of life. Zolmitriptan, a selective serotonin receptor agonist, is widely prescribed for acute migraine relief. However, it suffers from limited oral bioavailability due to hepatic first-pass metabolism, rapid clearance, and delayed onset of action, particularly during migraine-associated gastrointestinal disturbances. These limitations have led to the development of new delivery strategies to improve zolmitriptan’s effectiveness and patient outcomes. This review provides a comprehensive analysis of zolmitriptan delivery systems, classified into two developmental phases. Phase I approaches focused on conventional transmucosal and transdermal systems, such as fast-dissolving oral films, sublingual tablets, buccal films, and adhesive patches, which successfully bypass first-pass metabolism and improve the onset of action. However, these delivery systems remain constrained by variable permeability and inconsistent absorption. Phase II strategies focus on nanotechnology-based formulations, including polymeric nanoparticles, solid lipid nanoparticles, bilosomes, novasomes, spanlastics, transferosomes, niosomes, terpesomes, nanostructured lipid carriers, and nanolipomers. These platforms demonstrated superior brain-targeting potential, prolonged pharmacological effects, and higher bioavailability compared to traditional formulations. Special emphasis is placed on non-invasive routes such as intranasal, buccal, and transdermal administration, which offer rapid migraine relief, sustained efficacy, and improved patient adherence. Stepwise innovation in zolmitriptan delivery has progressed from conventional dosage forms to advanced nanocarriers that enhance bioavailability, brain targeting, and clinical efficacy. Future research should focus on patient-tailored delivery strategies, smart responsive carriers, and drug combinations that lower recurrence and improve long-term results. These advances can make migraine treatment more effective and practical.