Phase behavior of rifampicin in cholesterol-based liquid crystals and polyethylene glycol

Abstract

The phase behavior of rifampicin in cholesteryl-based carbonate esters (CCEs), cholesterol and polyethylene glycol4000 (PEG4000) was determined to evaluate their potential in the formulation of dry powder inhalation dosage forms. To guide the identification of the most suitable liquid crystalline system for the solubilization of rifampicin, the dielectric constants were evaluated. Thereafter, the phase behavior of various mixtures were characterized by polarized light microscope (PLM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Among the mixed-carrier systems, the cholesteryl cetyl carbonate (CCC) and PEG4000 system at 1:1 mole ratios yielded a homogeneous mixture with relatively high rifampicin content. This result was consistent with the prediction based on the dielectric constants. The phase diagram contained a eutectic point at CCC:PEG4000 (1:1) and 50 °C. Finally, the rifampicin drug was successfully incorporated into CCC and PEG system at a 1:6:6 mole ratio. Such a system would be amenable for oral inhalation.