Frovatriptan Succinate

Frovatriptan succinate is a 5-HT1B/1D receptor agonist approved for acute migraine treatment in adults. It has high affinity for serotonin receptors and demonstrates greater selectivity for cerebral arteries over coronary arteries, offering a potential advantage for patients at risk of coronary artery disease. Its distinguishing feature is a long elimination half-life of approximately 25 hours, substantially longer than other triptans, making it suitable for migraines of long duration or those prone to recurrence. Oral bioavailability is 20-30%, and the drug is metabolized by CYP1A2. Clinical trials showed 2-hour headache response rates of 38-40% for the 2.5 mg dose versus 22-35% for placebo. Headache recurrence at 24 hours was low at 9-14%.

Frovatriptan succinate-loaded polymeric nanoparticles (PNPs) were developed for brain targeting via intranasal administration. A double emulsion method and central composite design optimized the formulation. The nanoparticles were spherical and smooth. In vitro release showed an initial burst followed by sustained release over 72 hours. Ex vivo permeation across goat nasal mucosa was approximately three times higher than pure drug solution. Histopathology confirmed the safety of PNPs on nasal mucosa. Fluorescence microscopy in male Wistar rats demonstrated significantly higher brain uptake of PNPs at 30 minutes after intranasal administration compared to intravenous delivery, indicating rapid nose-to-brain transport. The formulation was stable over three months. This approach offers a promising strategy to improve frovatriptan’s onset of action, bioavailability, and brain targeting while reducing systemic side effects.

Fig. 1 SEM and AFM image of Frovatriptan succinate-loaded polymeric nanoparticles. (Deepika D.; et al. 2019)