Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin : 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin.

Abstract

Rifampicin (RFP) solutions, intended to reduce incidence of prosthetic graft infection, were prepared as three-dimensional ground mixtures (3DGMs) using β-cyclodextrin (βCD) and γ-cyclodextrin (γCD) and characterized for their spectroscopic properties and solubility. Phase solubility diagrams revealed that 3DGMs (RFP/βCD and RFP/γCD) produced a complex at 1:1 molar ratio. Pulsed field gradient nuclear magnetic resonance experiments indicated that the diffusion coefficients for RFP/βCD and RFP/γCD were similar to the respective diffusion coefficients for βCD and γCD. Rotating-frame Overhauser effect spectroscopy NMR spectra revealed the existence of a new exchanger peak for RFP/γCD, suggesting an intermolecular interaction different from that of RFP/βCD. Differential scanning calorimetry confirmed the presence of endothermic peak at 191°C indicating the manifestation of RFP in the inclusion complex. Interestingly, molecular interactions from the complexes, RFP/βCD and RFP/γCD, revealed different patterns of inclusion in the 3DGMs. In RFP/βCD, nuclear Overhauser effect spectroscopy NMR spectra indicated cross peaks for the protons of the methyl group of RFP and the protons (H-5 and H-6) in the βCD cavity. The methyl group of RFP interacted with the narrow rim of βCD. With RFP/γCD, cross peaks were due to the protons of the methyl group of RFP and the protons of the cavity of γCD suggesting multiple inclusion patterns. The observed multiple cross peaks affirm the inclusion of RFP into the CD cavity which enhanced its solubility by 1.6-2.0-fold when prepared as 3DGMs as RFP/βCD and RFP/γCD, respectively.