The affinity of irbesartan (IRB) to form inclusion complexes with beta-eyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and gamma-cyclodextrin (gamma-CD) was investigated in aqueous buffered solutions at pH 1.7, 4.1, and 7.0. Analysis of the UV absorption-pH profiles revealed that IRB has two p K-a values: p K-a1 = 3.60 (imidazolinone ring moiety) and p K-a2 = 4.70 (tetrazole moiety). In the presence of 5.0 mmol L-1 beta-CD, the tetrazole moiety became more acidic, indicating its inclusion within the beta-CD cavity. Phase-solubility diagrams (PSDs) were obtained for IRB in aqueous buffered solutions of beta-CD, HP-beta-CD, and gamma-CD at pH 4.1 (zwitterionic IRB), pH 1.7 (protonated IRB), and pH 7.0 (deprotonated IRB). Rigorous nonlinear regression analysis of IRB/CD PSDs at pH 4.1, where IRB is poorly soluble, yielded estimates of complex formation constants (K-11) that followed the decreasing order of HP-beta-CD >gamma-CD >beta-CD. The highest solubility enhancement of IRB was achieved by complexation with HP-beta-CD at pH 4.1. The formation of the IRB/beta-CD inclusion complex in solution and in the solid state has been proven through NMR, DSC, FT-IR, and XRD studies. Analysis of H-1 and C-13-NMR spectra indicated the inclusion of the tetrazole-biphenyl moiety within the beta-CD cavity.