Development and Evaluation of Tizanidine Hydrochloride-Loaded Nano-structured Lipid Carriers in Mucoadhesive Buccal Films for Enhanced Permeation

Abstract

The present study aimed to formulate and evaluate Tizanidine Hydrochloride-loaded nanostructured lipid carriers (NLCs) incorporated into mucoadhesive buccal films for sustained drug delivery. Tizanidine Hydrochloride is a centrally acting muscle relaxant with a short half-life and extensive first-pass metabolism. Nanostructured lipid carriers were prepared using glyceryl monostearate as the solid lipid, Capryol® 90 as the liquid lipid, Tween® 80 as the surfactant, and Poloxamer 188 as the co-surfactant. The optimized NLC formulation, TF4, showed a particle size of 182.3 ± 2.9 nm, a polydispersity index of 0.214 ± 0.012, a zeta potential of −31.6 ± 1.4 mV, entrapment efficiency of 89.6 ± 0.9%, and drug loading of 7.52 ± 0.09%. The optimized NLCs were incorporated into mucoadhesive buccal films using hydroxypropyl methylcellulose E15 and Carbopol 934P. Among the prepared films, BF5 exhibited satisfactory physicochemical and mechanical properties, including a thickness of 0.138 ± 0.004 mm, folding endurance of 174 ± 5 folds, surface pH of 6.18 ± 0.05, and drug content of 98.64 ± 0.72%. The formulation achieved 91.4% cumulative drug release over 8 hours. Release kinetic analysis showed the best fit with the Higuchi model ((R^2 = 0.9982)), suggesting diffusion-controlled release. Three-month stability studies showed that the optimized film retained satisfactory physical and physicochemical characteristics. These findings indicate that NLCbased mucoadhesive buccal films may offer a promising approach for the sustained delivery of Tizanidine Hydrochloride. Further permeation and in-vivo studies are required to establish their therapeutic performance.