New drug entities with poor aqueous solubility are becoming more prevalent as result of high-throughput screening in drug discovery. Poor aqueous solubility presents significant challenges, as it reduces the absorption and oral bioavailability. Several formulation approaches have been employed to overcome the limitations of low dissolution rate and/or solubility including; pH-adjustment, co-solvents, surfactants, inclusion complexes, lipid-based formulations i.e. Solid lipid nanoparticles (SLNs) and Nanostructured lipid carriers (NLCs), and nano-suspensions. In this study efforts are made for the selection of formulation approach based on the drug properties and the required specifications of the final dosage form. Among these formulation approaches solid lipid nanoparticles were selected with the aim of improving solubility/bioavailability of the poorly water-soluble drugs; BCS-II (Niclosamide) and BCS-IV (Sulfasalazine). Two different techniques i.e. Micro-emulsion Technique and Solvent Emulsification Diffusion Technique were used to fabricate SLNs. The SLNs formulations were characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (P-XRD) and Fourier Transform Infrared (FT-IR). The SLNs formulations loaded with Niclosamide and Sulfasalazine were successfully converted to solid dosage form followed by similarity study. In-vitro studies of SLNs formulations in comparison with marketed dosage form showed improvement in solubility and dissolution while the in-vivo studies confirmed improved oral bioavailability. Niclosamide loaded SLNs fabricated by Micro Emulsion Technique having particle size 204.2 ± 2.2 nm, polydispersity index 0.328 ± 0.02, zeta potential -33.16 ± 2mv, entrapment efficiency 84.4 ± 0.02%, and drug loading capacity 5.27 ± 0.03% were obtained. Different kinetic models showed zero order kinetics and Case-II transport mechanism. In-vivo pharmacokinetic study showed 2.15-fold increase in peak plasma concentration for Niclosamide loaded SLNs while relative bioavailability (Fr) of 11.08. Fabrication of Niclosamide loaded SLNs using Solvent Emulsification Diffusion Technique showed particle size 208.6 ± 2.2 nm, polydispersity index 0.376 ± 0.04, zeta potential -34.11 ± 1.2 mv, entrapment efficiency 85.4 ± 0.04% and drug loading capacity 3.18 ± 0.04 %. Observed zero order kinetics with case-II transport, the range in the parenthesis might be helpful for the drug release mechanism. 2.04-fold increase in peak plasma concentration was observed in pharmacokinetic study with relative bioavailability (Fr) of 10.59. In case of Sulfasalazine-SLNs prepared by Micro Emulsion Technique having particle size 217.2 ± 3.2nm, PDI 0.373 ± 0.02, zeta potential -35.26 ± 2mV, entrapment efficiency 89.1 ± 0.03% and drug loading capacity 2.87 ± 0.05% were obtained. Kinetic modelling studies showed mixed order kinetics for drug release. Release exponent was more than 0.89, regarded as Super Case-II diffusion mechanism. In-vivo pharmacokinetic study showed 2.43-fold increase in oral bioavailability of sulfasalazine as SLN formulation compared to commercial product. Solvent Emulsification Diffusion Technique was used to fabricate Sulfasalazine loaded SLNs, showed particle size 202.3 ± 2.2 nm, PDI 0.376 ± 0.02, zeta potential -35.82 ± 2 mV, entrapment efficiency 86.3 ± 0.02% and drug loading capacity 3.03 ± 0.04%. Zero order kinetics and Case-II transport mechanism for drug release was observed with 1.86-fold increase in peak plasma concentration during pharmacokinetic study. These studies validated that, SLNs as nanoparticulate drug delivery system enhanced oral bioavailability of Niclosamide and Sulphasalazine. Hence, these studies provide new strategies for the oral bioavailability of hydrophobic drugs.