The thermodynamic characterization of host-guest complex formation processes based on modified cyclodextrins (CDs) presents several difficulties that are absent when using native CDs. They are mainly due to the relatively wide distribution of the degree of molecular substitution and also to the indeterminacy in the location of the modified groups. A more common trouble would arise from the coexistence of coupled processes, such as CD-surfactant complexation and surfactant demicellization. In the present work a reasonable approach based on the analysis of isothermal titration calorimetric measurements is employed to assess the effect of the number of molecular substitutions as well as of the CD cavity size in supra-molecular complexes formed by 2-hydroxypropyl-CDs and n-octyl-beta-D-glucopyranoside. The employed method considers both first- (1:1) and second-order (1:2 and 2:1) stoichiometries. The results were significantly different from those previously observed for native CDs. The substituted groups increase entropically the stability of 1:1 species based on alpha-CD, while compete with the surfactant for the CD cavity in the case of 1:1 and 1:2 species based on beta- and gamma-CD, respectively. Also, the modified beta-CD seems to enhance the formation of non-inclusion second-order complexes. (c) 2013 Elsevier Ltd. All rights reserved.