Objective: One of the greatest challenges drug formulation is facing is poor bioavailability via oral route. In this regard, nasal drug delivery has been commonly used as an alternative route to improve drug bioavailability. Nefopam hydrochloride (NF) is an analgesic drug that suffers from poor bioavailability due to extensive metabolism in liver. Accordingly, the goal of the present study was to improve NF bioavailability via niosomal-based formulation designed for intranasal delivery.
Materials and methods: Vesicles were developed by mixing surfactants (Span 20, Span 40, Span 80, and Span 85) at four molar ratios of 1:1, 1:2, 1:3, and 1:4 of cholesterol to surfactant. Entrapment efficiency, particle size, zeta potential, release percentage, ex-vivo permeation parameters, and niosomes' stability were determined. Also, the pharmacokinetic parameters of the optimized formula in in-situ gel base were measured in rats.
Results: Niosomes showed entrapment efficiency .80%, particle size ,550 nm, and zeta potential ranging from -16.8±0.13 to -29.7±0.15. The produced vesicles showed significantly higher amounts of drug permeated across nasal mucosa (2.5 folds) and prolonged NF release compared with NF solution. Stability studies of optimum formula showed nonsignificant changes in niosomes parameters over a storage period of 6 months. The in-vivo studies showed a 4.77-fold increase in bioavailability of optimized nasal niosomes compared with oral solution of drug.
Conclusion: The obtained results revealed the great ability of the produced NF-loaded nio-somes to enhance drug penetration through nasal mucosa and improve its relative bioavailability compared with NF oral solution.
Keywords: intranasal permeation; nefopam hydrochloride; niosomes; nonopioid analgesics; optimization.