Preparation, characterisation, and testing of reservoir-based implantable devices loaded with tizanidine and lidocaine

Abstract

Multiple sclerosis is a chronic neuroimmunological disorder that causes progressive disability, primarily in young adults. It places a significant burden on healthcare systems due to high medication costs and long-term care needs. Implantable devices offer a promising alternative for delivering sustained drug doses in the treatment of chronic conditions. This study introduces a novel long-acting subcutaneous implant for dual-drug delivery: tizanidine (TZ) for spasticity management and lidocaine (LD) for post-insertion pain relief. Reservoir-type implants were developed with TZ in the core and LD in the shell. Two fabrication methods—direct compression and vacuum compression moulding (VCM)—were evaluated for TZ-loaded pellets (3 mm diameter, ~ 10 mm length) using TZ base and TZ hydrochloride. Pellets were encapsulated inside a biodegradable polycaprolactone (PCL) tubular membrane to control drug release. Direct compression pellets, made with poly(vinyl pyrrolidone) and hydroxypropyl-β-cyclodextrin, disintegrated quickly, releasing TZ over 20 days. VCM pellets, formulated with PCL or PCL/poly(ethylene glycol) (PEG), offered prolonged release: up to 200 days for TZ base and 80 days for TZ hydrochloride. Adding PEG accelerated TZ release, reducing duration to 20 days (TZ base) and 125 days (TZ hydrochloride). LD was incorporated into the PCL membrane, providing up to three days of sustained release. Physicochemical analysis confirmed formulation homogeneity and no covalent interactions. These findings highlight the potential of this implant system for MS-related spasticity management, supporting further research into long-acting implants to improve treatment adherence and patient outcomes. Graphical Abstract

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