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The purpose of this study was to employ the Hot melt extrusion technique (HME) to prepare amorphous solid dispersions (ASDs) of Apremilast, a BCS class IV drug. Drug–polymer miscibility was assessed with solubility parameter and the Flory-Huggins equation. Soluplus® was selected as the carrier and solid dispersions were prepared in 10:90, 30:70 and 50:50 drug: polymer ratios. The study evaluated the influence of drug loading and extrusion temperature on the solid dispersions. The produced solid dispersion were characterized using FTIR, DSC and XRD. Pharmacokinetics of Apremilast following oral delivery of the solid dispersion formulations were predicted in silicousing GastroPlus™. The extruder processing temperature had a profound influence on the generation of ASDs. Solid-state characterization exhibited amorphous nature of drug in the solid dispersion samples. The constructed in silicomodel predicted more than 50% of increase in Apremilast Cmax and AUC values from solid dispersion formulations compared to plain Apremilast. In conclusion, the Apremilast ASDs formulated with Soluplus® showed a significant increase in solubility and may be considered as a favorable approach for enhancing Apremilast oral bioavailability. Stress samples stored at 25 °C/75% RH condition for 10 days showed decrease in dissolution profile for ASDs with 50% and 90% Soluplus® and no change was observed in ASDs with 70% Soluplus®. Based on the conducted studies, an optimum drug: polymer ratio of 30:70 was suggested for Apremilast: Soluplus® ASDs for further development.