Effect of substituted cyclodextrins on ibrutinib solubility and characterization of IBR-cyclodextrin inclusion complexes by isothermal titration calorimetry in solution state

Abstract Ibrutinib (IBR) is a Bruton's tyrosine kinase inhibitor, a potent drug used in the treatment of various B cell malignancies. The IBR has poor bioavailability due to low aqueous solubility and high first-pass metabolism. The current research aims to enhance the IBR aqueous solubility by complexation with substituted beta-cyclodextrins and characterize the inclusion complexes using isothermal titration calorimetry. The complexation rate constants calculated from phase solubility study and isothermal titration calorimetry range from 1000 to 6600M −1 , indicating stable inclusion complexes' formation. The driving forces for the formation of inclusion complexes in the solution state are characterized by isothermal titration calorimetry. The thermodynamic parameters such as negative Gibbs free energy change, negative change in enthalpy values, and positive change in entropy values indicate that the formation of inclusion complexes is a spontaneous reaction.