title: Molecular encapsulation of rifampicin as an inclusion complex of hydroxypropyl-β-cyclodextrin: design; characterization and in vitro dissolution.
abstract: 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 0.5h. 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.
authors.affiliation: Medicine Engineering Research Center, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Qunyou
authors.initials: Q
authors.lastname: Tan
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D044367:Phase Transition / Q000187:drug effects; D012293:Rifampin / Q000737:chemistry* / Q000494:pharmacology*; D012995:Solubility / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D012293:Rifampin