Despite being the most effective hypolipidemic agent, poor physicochemical properties of Rosuvastatin calcium (RCa) remain challenging obstacles in the development of pharmaceutical dosage forms. Inclusion complexes (ICs) of RCa with cyclodextrin (CD) derivatives; methyl-beta-cyclodextrin (M-beta-CD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CD; Captisol(R)) were formulated by kneading and freeze-drying (lyophilization) methods. Pysicochemical properties of ICs were evaluated by SEM, DSC, XRD, FT-IR,H-1-NMR analyses. Entrapment efficiency (EE), water solubility,in vitrorelease analyses were also performed. Safety and efficacy of the ICs were analyzed by cytotoxicity and permeation studies on Caco-2 cell lines. Both CDs indicated A(L)type phase solubility diagrams showing that [1:1] molar ratio. Apparent stability constants (K-1:1) were found to be 60.93 M(-1)for M-beta-CD and 158.07 M(-1)for Captisol(R). High EE in the range of 93.50-105.40% was achieved. Molar solubility of RCa was increased 3.7- and 4.1-fold with M-beta-CD and Captisol(R)ICs, respectively.In vitrorelease analyses have indicated the equivalence of dissolution profiles for M-beta-CD and Captisol(R)based ICs to that of pure RCa (f(2)> 50). Cytotoxicity studies on Caco-2 cell lines have revealed the safety of ICs for oral use. Permeability studies demonstrated that selected lyophilized F6 formulation has shown the best permeation rate with P(app)value of 3.08 x 10(-7)cm center dot s(-1). Considering greater water solubility, lower toxicity, high efficiency of complexation as well as, RCa-like permeability andin vitrorelease behavior at pH 6.8; Captisol(R)based lyophilized F6 formulation was selected as the best IC to be used in oral dosage forms of RCa.