Cefuroxime Axetil (CA) is a poorly soluble, broad spectrum antibiotic which undergoes enzymatic degradation in gastrointestinal tract. The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery systems containing CA using hot-melt extrusion (HME) to improve absorption. Selected formulations of CA and lipids were extruded using a twin screw hotmelt extruder. Milled extrudates were characterized for dissolution, floating strength, and micromeritic properties. Solid-state characterization was performed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and hot-stage microscopy. In vitro characterization demonstrated that the *