In this study, we examined the effect of pharmaceutical excipients preferred in lipid-based formulations for lymphatic delivery on in vitro association of probucol with chylomicron (CM). CM stability study was performed under the conditions of room temperature, refrigeration and deep freezing to optimize the storage condition of CM dispersion prior to CM-binding study. The mean particle size, size distribution and zeta potential value were considerably maintained for 48 h under the refrigeration condition. CM-binding study was conducted using probucol incorporated in vehicles composed of solubilizer (Transcutol HP or ethanol or propylene glycol) or surfactant (Tween-80 or Tween-20 or Cremophor ELP), and CM dispersion obtained by a density-gradient ultracentrifugation. Levels of the association of probucol with CM were largely governed by solubility of probucol in pharmaceutical excipients tested in this study, and the ability of solubilizers tested to enhance the affinity of probucol with CM was much greater than that of surfactants tested. Furthermore, the association of probucol with CM was enhanced by increasing the amount of the drug solubilized in propylene glycol or Transcutol HP. Together, the result of this CM-binding study showed that solubilizers tested in this study can increase levels of the association of probucol with CM, potentially leading to an increase in lymphatic exposure of drugs. Thus, identifying pharmaceutical excipients having better solubilizing ability would be advantageous for enhanced lymphatic delivery.
Keywords: Chylomicron; lymphatic delivery; pharmaceutical excipient; probucol; solubilizer; surfactant.