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Background <p>Lasmiditan is a selective serotonin 5-HT₁F receptor agonist used in migraine treatment, but its oral therapy is often limited by inadequate bioavailability. The present work focused on the development of a Lasmiditan-loaded Nanostructured Lipid Carrier (NLC) formulation to enhance the oral delivery and pharmacokinetic performance of Lasmiditan.</p> Method <p>The Lasmiditan-loaded NLCs were prepared using an optimised blend of solid and liquid lipids, guided by a Box–Behnken design, with the addition of a surfactant. The optimized formulation was systematically characterised for entrapped drug, particle size, Size distribution, surface charge, in vitro release behaviour, and storage stability. In vivo pharmacokinetic parameters, including AUC, C<sub>max</sub>, T<sub>max</sub>, half-life, volume of distribution, and clearance, were evaluated.</p> Results <p>The optimised formulation revealed a particle size of 201&#xa0;nm, uniform size distribution of 0.388, stable surface charge (-32.45mV), and high drug encapsulation of 85.15%. In vitro release studies indicated a prolonged and controlled release pattern with cumulative release of 81.71% at end of 24&#xa0;h. Kinetic modelling revealed a non-Fickian transport mechanism. Stability assessment under long-term and accelerated storage conditions showed minimal changes in physicochemical parameters over 180 days, confirming the formulation’s stability. Pharmacokinetic evaluation demonstrated significantly higher systemic exposure of Lasmiditan-loaded NLC formulation compared to the drug-suspension comparator, as reflected by an increased cumulative drug exposure derived from the plasma concentration–time relationship.</p> Conclusion <p>The NLC formulation exhibited a 1.7-fold increase in systemic exposure compared to the oral standard, with faster onset and sustained release, suggesting its potential as an effective strategy to enhance the oral therapeutic efficacy of Lasmiditan in migraine management.</p>

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Development and Optimization of Lasmiditan-Loaded Nanostructured Lipid Carriers for Enhanced Oral Bioavailability

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • Krutuja R. Chougule,
  • Archana Patil,
  • Sheetal Patil,
  • Ravikiran Kanabargi

摘要

Background

Lasmiditan is a selective serotonin 5-HT₁F receptor agonist used in migraine treatment, but its oral therapy is often limited by inadequate bioavailability. The present work focused on the development of a Lasmiditan-loaded Nanostructured Lipid Carrier (NLC) formulation to enhance the oral delivery and pharmacokinetic performance of Lasmiditan.

Method

The Lasmiditan-loaded NLCs were prepared using an optimised blend of solid and liquid lipids, guided by a Box–Behnken design, with the addition of a surfactant. The optimized formulation was systematically characterised for entrapped drug, particle size, Size distribution, surface charge, in vitro release behaviour, and storage stability. In vivo pharmacokinetic parameters, including AUC, Cmax, Tmax, half-life, volume of distribution, and clearance, were evaluated.

Results

The optimised formulation revealed a particle size of 201 nm, uniform size distribution of 0.388, stable surface charge (-32.45mV), and high drug encapsulation of 85.15%. In vitro release studies indicated a prolonged and controlled release pattern with cumulative release of 81.71% at end of 24 h. Kinetic modelling revealed a non-Fickian transport mechanism. Stability assessment under long-term and accelerated storage conditions showed minimal changes in physicochemical parameters over 180 days, confirming the formulation’s stability. Pharmacokinetic evaluation demonstrated significantly higher systemic exposure of Lasmiditan-loaded NLC formulation compared to the drug-suspension comparator, as reflected by an increased cumulative drug exposure derived from the plasma concentration–time relationship.

Conclusion

The NLC formulation exhibited a 1.7-fold increase in systemic exposure compared to the oral standard, with faster onset and sustained release, suggesting its potential as an effective strategy to enhance the oral therapeutic efficacy of Lasmiditan in migraine management.