||The present study was focused on comparing different methods of preparations and the effect of hydroxy propyl beta cyclodextrin (HPßCD) and randomly methylated beta cyclodextrin (RMßCD) in enhancing dissolution and oral bioavailability of poorly soluble, antiretroviral protease inhibitor, ritonavir. Complexes of ritonavir-CD complexes were prepared at 1:1 ratio using physical mixing, co evaporation, spray drying and freeze drying methods. The prepared complexes were characterized using FTIR, differential scanning calorimetry (DSC), x-ray diffraction studies (XRD), nuclear magnetic resonance spectroscopy (NMR) and scanning electron microscopy. In vitro dissolution studies were performed in 0.1N HCl and the dissolution data were subjected to one way ANOVA. Phase solubility studies proved complexation of ritonavir and were of AL type. All complexes showed enhanced dissolution rate compared to ritonavir but the complex prepared with RMßCD using freeze drying had shown complete and fast drug release. On the basis of above results, it was concluded that complex prepared with RMßCD by freeze drying was successful in improving solubility, dissolution rate and oral bioavailability of ritonavir.