Exemestane (EXE) is an irreversible aromatase inactivator used for the treatment of advanced postmenopausal breast cancer. EXE is orally active but its bioavailability is about 5% due to its low solubility in water and the extensive first pass effect. It is known that cyclodextrin (CD) complexation enhances solubility and oral bioavailability of poorly soluble drugs. Thus, it was aimed to design and develop cyclodextrin complexes in powder and tablet forms containing EXE to improve aqueous solubility and in vitro permeability. In this study, inclusion complexes of EXE were prepared with three different CD derivatives (methyl-beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin) and by two different preparation methods (kneading and colyophilization) and the complexes were characterized with H-1 NMR, FT-IR, SEM, X-ray and DSC analyses. Both inclusion complexes and tablet formulations prepared using EXE:CD inclusion complexes showed significant improvement in the dissolution profile of this oral antiestrogen drug. Furthermore, Caco-2 cell permeation studies revealed that apparent permeability constant for EXE was increased by 3-fold via cyclodextrin complexation. In conclusion, complexation of EXE with cyclodextrin derivatives, randomly methylated-beta-cyclodextrin in particular, results in a more efficient tablet formulation with improved dissolution and better permeation suggesting an enhancement in oral bioavailability of the drug. (C) 2010 Elsevier B.V. All rights reserved.