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Abstract

Tizanidine (TZ) is a selective α2-adrenergic agonist used to relieve spasticity associated with spinal cord injury and multiple sclerosis. Despite its clinical utility, TZ is a Biopharmaceutics Classification System Class II drug with poor aqueous solubility and an oral bioavailability of about 13%, limiting efficacy. Polymeric nanotechnology was employed to enhance dissolution and absorption. TZ nanoparticles were prepared by a solvent–antisolvent method using carriers Soluplus® (SL) and Poloxamer 188 (PL188) with co-stabilizers such as PEG 200 and glycerol; TZ-NP formation succeeded with SL but not with PL188. The optimized formulation, F6 (TZ:SL 1:1 with glycerol at 50% w/w of SL), achieved a particle size of 89.88 nm, a narrow PDI of 0.2517, drug content 98.4%, and entrapment efficiency 98.5%. F6 delivered complete drug release within 75 minutes, far exceeding the 40% release from unformulated TZ. To enable rapid onset, F6 NP was lyophilized with 3% mannitol and incorporated into sublingual tablets with various superdisintegrants. The optimized tablet, SL3, disintegrated within 40 seconds and achieved 100% drug release within 5 minutes, indicating markedly improved dissolution and potential for enhanced bioavailability and patient compliance. This study demonstrates that Soluplus-based TZ nanoparticles, followed by lyophilization and sublingual formulation, offer a viable strategy to overcome TZ’s solubility and bioavailability limitations, enabling faster onset of action and improved therapeutic outcomes‎.

Keywords: Tizanidine, Soloplus®, Poloxamers 188, PEG200, Glycerol

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