Molecular Simulation of the Complexes Formed by Hydroxypropyl-β-Cyclodextrin and Rifampicin with Different Solvents

Hydroxypropyl-β-cyclodextrin (HPβCD) is a derivatized cyclodextrin in which several H atoms on the hydroxyls of the glucose rings are substituted by 2-hydroxypropyl groups. The cyclic structure of HPβCD creates a cavity capable of totally or partially enclosing different molecules (inclusion complexes), and this capacity makes it useful in the pharmaceutical industry. Rifampicin is an antibiotic commonly used to treat tuberculosis; however, some of its properties such as its low solubility and variable bioavailability need to be improved by encapsulating it in systems such as HPβCD. The inclusion complexes formed by twelve structures of HPβCD and rifampicin with various polar and non-polar solvents are studied using molecular simulation. Diverse solvents are simulated using the zwitterionic or neutral configuration of rifampicin, and different values of relative permittivity in the electrostatic contribution to the total energy. The latter constant has little effect on the formation of inclusion complexes, whereas the type of rifampicin essentially determines the energies and configurations of the complexes. The zwitterion is located near the primary rim of HPβCD and the neutral form of rifampicin is near the secondary one. In both cases, the piperazine tail is incorporated into higher-energy complexes inside the host.