Formulation and Characterization of Tizanidine HCl Loaded Controlled Release Mesoporous Silica Nanoparticles (MSNs)

Introduction: Spasticity is a disorder in which continuous contraction of certain muscles leads to muscle stiffness. Tizanidine, a frequently prescribed skeletal muscle relaxant for spasticity treatment, exhibits a short elimination half-life and limited oral bioavailability. The aim of current study is to prepare controlled-release microparticles incorporating tizanidine-loaded Mesoporous Silica Nanoparticles (MSNs) for enhancing the bioavailability, to treat spasticity. Materials and Methods: The MSNs were synthesized via a sol-gel technique with slight modification, with drug loading using the solvent impregnation method. Design expert software was used and box-behnken design was selected for the optimization of MSNs. The effect of TEOS (silica precursor), CTAB (surfactant), and NaOH (base catalyst) was analyzed on response variables. For controlling the release of tizanidine from MSNs, the tizanidine-loaded MSNs were incorporated in polymeric microparticles. Results: The optimized batch of MSNs exhibited a mean particle size of 131.7 nm, a Polydispersity Index (PDI) of 0.202, a Zeta Potential (Z.P.) of 30.6 mV, and an Entrapment Efficiency (EE%) of 51.18%. Additionally, the optimized MSN formulation underwent SEM, DSC, and XRD analyses. The polymeric microparticles containing tizanidine-loaded MSNs were evaluated for particle size, microscopic evaluation, and in vitro drug release. The microparticles demonstrated 12% initial rapid release followed by a sustained release pattern for 10 hr and exhibited the Higuchi Model with a regression coefficient (R2) of 0.9682. Conclusion: The developed polymeric microparticles, incorporating tizanidine-loaded mesoporous silica nanoparticles, exhibited a controlled drug release profile, facilitating the enhancement of the drug's oral bioavailability. Consequently, a reduction in dosing frequency is anticipated, leading to improved patient compliance.