Molecular encapsulation of rifampicin as an inclusion complex of hydroxypropyl-β-cyclodextrin: Design; characterization and in vitro dissolution

A hydrophobic drug, rifampin (RFP), was molecularly encapsulated into hydroxylpropyl-β-cyclodextrin (HCD) to form a molecular inclusion complex (MRICD) with higher solubility and stability. A solid-state grinding method was applied to prepare MRICD for 0.5 h. The inclusion ratio, binding constant and the change of Gibbs free energy estimated from the phase solubility diagram and/or by the ultraviolet–visible spectroscopic method were 1:1, ∼218 mol/L and −1.767 KJ/mol, respectively. Differential scanning calorimetry and Fourier transformed infrared spectra of MRICD confirmed the molecular interactions between RFP and HCD. Morphological differences between MICDH and RFP further confirmed the molecular encapsulation of RFP. The most probable configuration of MRICD was estimated via computer simulation. MRICD had a higher dissolution rate than free RFP. Weibull function fit well the dissolution data of MRICD. Broth macrodilution experiments indicated that MRICD had good antibacterial activity. MRICD might be a promising system for oral or parenteral drug delivery to treat bacterial infections.

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► MRICD was prepared for only 0.5 h by solid-state grinding method.
► Physical properties and antibacterial activity were systematically evaluated.
► MRICD improved solubility and stability of RFP.
► MRICD enhanced physical properties, meanwhile having good antibacterial activity.