In Vivo Evaluation of Almotriptan malate Formulation through Intranasal Route for the Treatment of Migraine: Systematic Development and Pharmacokinetic Assessment

Migraine headaches are usually intolerable, and a quick-relief treatment remains an unmet medical need. Almotriptan malate is a serotonin (5-HT 1B/1D ) receptor agonist approved for the treatment of acute migraine in adults. It is currently available in an oral tablet dosage form and has a T max of 1–3 h, and therefore, there is a medical need to develop a non-invasive rapidly acting formulation. We have developed an intranasal formulation of almotriptan malate using the quality-by-design (QbD) approach. A 2-factor 3-level full factorial design was selected to build up the experimental setting. The developed formulation was characterized for pH, viscosity, in vitro permeation, ex vivo permeation, and histopathological tolerance. To assess the potential of the developed formulation to produce a rapid onset of action following intranasal delivery, a pharmacokinetic study was performed in the Sprague–Dawley rat model and compared to the currently available marketed oral tablet formulation. For this, the LC–MS/MS bioanalytical method was developed and used for the determination of plasma almotriptan malate concentrations. Results of a pharmacokinetic study revealed that intranasal administration of optimized almotriptan malate formulation enabled an almost five-fold reduction in T max and about seven-fold increase in bioavailability in comparison to the currently available oral tablet formulation, suggesting the potential of developed almotriptan malate intranasal formulation in producing a rapid onset of action as well as enhanced bioavailability. Graphical Abstract