Immediate- and Extended-Release Hot-Melt Extruded Ocular Inserts for Levofloxacin Hemihydrate: Formulation Development, Optimization, and In Vitro Evaluation (Part I)

Levofloxacin (LFX) is widely prescribed to treat bacterial ocular infections. However, its topical application as eyedrops faces rapid precorneal clearance and poor ocular surface residence. These limitations often require frequent administration. In this project, ocular inserts loaded with LFX were developed using hot-melt extrusion (HME) to address these shortcomings. A D-optimal mixture design was applied to study the effects of hydroxypropyl cellulose (HPC-JXF), polyethylene oxide (PEO-N10), and sorbitol on LFX-release behavior. Sixteen insert formulations were prepared and evaluated for their physicochemical characteristics and in vitro dissolution performance. All developed inserts showed adequate weight uniformity, thickness, surface pH, and drug content. Statistical analysis results revealed that formulation composition had a marked influence on LFX release at both 0.5 and 8 h time points. PEO-N10 played a key role in improving LFX release; however, HPC-JXF contributed to release retardation and preservation of matrix integrity. Numerical optimization identified a formulation containing 90% polymer content of HPC-JXF and 10% LFX as the optimal extended-release system. The optimized formulation released ~18% of LFX within the first 30 min and ~64% at 8 h, indicating close agreement between the experimental results and model-predicted values. Differential Scanning Calorimetry thermograms suggested that HME processing helped in the molecular dispersion of LFX throughout the polymeric carrier, resulting in an amorphous drug distribution within the insert matrix. The Korsmeyer–Peppas release exponent, determined via DDSolver modeling, indicated anomalous transport, where drug diffusion and polymer relaxation contributed to the release process. Overall, the project outcomes prove the potential of HME for the fabrication of LFX-loaded ocular inserts with tunable release characteristics that range from immediate to extended release. The optimized insert formulation could be a promising alternative platform to conventional ophthalmic eyedrops for the management of bacterial ocular infections.