Background: Fingolimod hydrochloride (FH) has emerged as a vital medication for managing Multiple Sclerosis (MS). Despite its high oral bioavailability of 93%, it is plagued by slow oral absorption (T = 8-12 h) and extensive hepatic metabolism. Intranasal administration has emerged as an alternative to address these limitations, ensuring efficient central nervous system delivery and minimizing peripheral exposure and first-pass metabolism.
Objective: This study aims to develop and evaluate FH nasal films for enhanced drug delivery.
Methods: A Design of Experiments approach was employed to formulate FH nasal films, utilizing HPMC E50 as a film-forming polymer, PEG 400 as a plasticizer, and Me-β-CD as a permeation enhancer. Two formulations with superior in vitro and ex vivo performance were selected for in vivo evaluation. A comparative pharmacokinetic study was conducted in C57BL/6 J mice in the brain and serum after administration of nasal films and oral FH solution, respectively. Sparse sampling and non-compartmental analysis were used.
Results: FH nasal films efficiently delivered the drug to both serum (C = 0.35 ± 0.021, C = 0.38 ± 0.029 μg/mL) and brain (C = 0.39 ± 0.05, C = 0.44 ± 0.048 μg/mL), achieving higher levels than oral delivery. Brain relative bioavailability (% F) was 519% and 534%, while serum % F was 295% and 343%.
Conclusions: The rapid nose-to-brain delivery within 30 min, in contrast to 10-h Tmax of the oral solution, indicates the potential of a combined IN and oral treatment regimen. This approach could expedite the attainment of steady-state concentrations, offering a promising method for managing multiple sclerosis (MS).
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