Purpose <p>This study aims to develop a stable solid self-double emulsifying drug delivery system (S-SDEDDS) for famotidine to improve its permeability and oral bioavailability (BA).</p> Methods <p>Drug solubility was determined in different vehicles. The oil-to-aqueous phase ratio in primary emulsion was optimized using pseudo-ternary phase diagrams. SDEDDSs (F1–F6) were prepared using two hydrophilic surfactants. Globule size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were determined. Among six formulations, F4 was optimized and converted to solid SDEDDS (SF4) with Neusilin US2. SF4 was further characterized using Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM), in vitro release, ex vivo permeation, and pharmacokinetic studies were conducted.</p> Results <p>The globule size, PDI, ZP, and EE of Liquid SDEDDSs (L-SDEDDSs) ranged from 197.1 ± 1.3&#xa0;nm to 362.3 ± 2.1&#xa0;nm, 0.22 ± 0.00 to 0.26 ± 0.03, -24.33 ± 0.73&#xa0;mV to -36 ± 0.36&#xa0;mV and 90.15 ± 0.61% to 95.12 ± 0.15%, and for SF4, 225.2 ± 4.2&#xa0;nm, 0.21 ± 0.03, -35.86 ± 0.75&#xa0;mV and 95.5 ± 0.14%, respectively. DSC and SEM studies indicated the absence of crystallinity in SF4. Famotidine release from Active Pharmaceutical Ingredient (API) and marketed tablet (Famocid 20) were 96.74 ± 0.01% and 99.95 ± 0.05%, respectively, in first 2&#xa0;h, and the SF4 filled hard gelatin capsules (00) released 50.27 ± 0.07% of drug in first 2&#xa0;h and 99.26 ± 0.21% in next 6&#xa0;h. SF4 showed a fourfold increase in flux over the drug solution. It was stable for 6&#xa0;months at room temperature. Pharmacokinetic studies in rats revealed 3.24 and 1.78-fold BA enhancement over the drug solution and tablet suspension. SF4 formulation exhibited level A in vitro-in vivo correlation.</p> Conclusions <p>A stable famotidine solid SDEDDS formulation (SF4) was developed and demonstrated to improve the oral BA.</p> Graphical Abstract <p></p>