Analysis of the molecular association of rifampicin with hydroxypropyl-β-cyclodextrin

Abstract

Inclusion complexes of rifampicin (RP) were prepared with hydroxypropyl-β-cyclodextrin (HPβCD). The aqueous solubility of RP increased linearly with cyclodextrin concentration in all range of the solubility diagram. The data was analyzed using the framework of Higuchi and Connors. The stability constant (K) values for RP/HPβCD complex at pH 6.9 were 18 and 120-125 M-1 for ionic strength 0.01 and 0.18M, respectively. The analysis of the chemical shift data of 1H and 15N for free RP and RP/HPβCD inclusion complex reveal that only peaks of the side chain related to the piperazine ring of RP change substantially, probably due to interaction of this region of RP molecule with the hydrophobic core of HPβCD. We also postulated the optimized structure of RP/HPβCD inclusion complex using molecular modelling study. We found that the postulated structure was in agreement with 1H and 13C-NMR and 15N-NMR spectra.