To conduct historical review on the clinical effects of a water-insoluble, mucoadhesive, formulation technology used to deliver granisetron, zolmitriptan and dihydroergotamine by the nasal route.

The nasal route is an attractive route of drug delivery, as the nasal cavity is lined with blood vessels that provide direct access to systemic circulation. However, absorption of drug compounds as formulated in the traditional liquid nasal sprays have been limited.  In the case of dihydroergotamine (DHE), the liquid nasal DHE product has slow and variable absorption and has limited the use of the product in at-home setting, and use of DHE remains primarily in the injectable form in the clinical setting. Thus, there is a need for a non-injectable form of DHE that enables efficacious systemic levels rapidly and consistently in the at-home setting. A formulation technology that increases absorption of DHE through the nose could enable a product that meets such a need.

The characteristics of the water-insoluble mucoadhesive formulation technology is reviewed, including historical results from human pharmacokinetic studies of granisetron and zolmitriptan nasal formulations utilizing the technology.  Then, the applicability of the technology for DHE is assessed based on the results of the human pharmacokinetic study.

Granisetron formulation showed 100% bioavailability compared to marketed granisetron IV injection.  Absorption was rapid with Cmax < 20 minutes after administration.  The zolmitriptan formulation showed higher and faster absorption than the marketed liquid nasal spray with 330% higher bioavailability in the first 2 hours after administration. 

The DHE formulation showed faster absorption than the marketed liquid nasal spray with 450% higher AUC in the first 30 minutes after administration.  Additionally, the DHE formulation showed substantially lower variability compared to the marketed liquid nasal spray.

The water-insoluble mucoadhesive formulation technology enables consistent and rapid Intranasal absorption of drugs including granisetron, zolmitriptan and DHE.