Objective: The present investigation was aimed to overcome the problems associated with the solubility, dissolution and oral bioavailability of ivacaftor by employing spray drying technology. Method: Ivacaftor solid dispersions were prepared by using copovidone, hypromellose 5CPs, soluplus were selected as a carriers and sodium lauryl sulphate was selected as surfactant. Drug and polymer ratio was chosen as 1:1 ratio and characterized the solid dispersions by differential scanning calorimetry (DSC), scanning electron calorimetry (SEM) and X-ray diffraction studies (X-RD), Fourier transform infrared spectroscopy (FT-IR) . Later solid dispersions were manufactured into tablets by direct compression method by using Acdi-sol as a super disintegrant and evaluated for their post compression parameters. Further optimization was done by employing the 2 2 full factorial design by selecting the copovidone (X1) and sodium lauryl sulphate (X2) as independent factors and invitro drug release (Y2) as a dependent factor. In addition the optimized formulation was carried out for its invivo evaluation by using rats. Results: Spray drying technology successfully employed to overcome the solubility problem by preparing the drug into their solid dispersions.DSC, SEM, X-RD and FT-UR performed on solid dispersion showed that ivacaftor existed in the amorphous form within the solid dispersion formulation fabricated using the spray drying process. Further design expert 12 software used to find the significant effect of independent factors on dependent factor by using 2D and 3D plots. Moreover, invivo study in rats also justified the improvement in the therapeutic efficacy of optimized formulation over pure drug. Conclusion: Thus, spray-dried technology can be an effective method for enhancing the bioavailability of ivacaftor