Quality by design-oriented formulation optimization and characterization of guar gum-pectin based oral colon targeted liquisolid formulation of xanthohumol

Abstract

In the present study a colon targeted liquisolid powder of xanthohumol was developed using Central Composite Design (CCD). Xanthohumol is a drug obtained from hops plants that can be effective in the treatment of UC. It possesses poor aqueous solubility, permeability and dissolution rate limited oral bioavailability. Hence, it was thought to enhance its dissolution rate by formulating liquisolid powder. Liquisolid technology is simple, single step and cost effective techniques to enhance dissolution rate of lipophilic drugs. Further, the formulation was targeted to colon using optimized combination of guar gum and pectin. Liquisolid powder of xanthohumol was formulated using Transcutol P as non-volatile solvent, polysaccharide mixture of guar gum and pectin as carrier, Syloid XDP as coating agent. The ratio of guar gum, pectin and Syloid XDP affecting angle of repose, drug loading and dissolution of drug in 5 h were optimized using CCD. The optimized formulation showed angle of repose of 26.78 degrees, drug loading of 89.34% and dissolution of drug in 5 h of 5.23%, respectively. The formulation showed site-specific release of liquisolid with less than 10% drug release in initial 5 h due to the release restricting property of guar gum and pectin followed by a burst release of xanthohumol between 5th and 12th hour indi-cating colon specific release of xanthohumol. The powder X-ray diffraction studies, differential scanning calo-rimetry and scanning electron microscopy revealed about complete solubility of xanthohumol in the Transcutol P and complete adsorption of the liquid on surface of Syloid XDP, guar gum and pectin. The accelerated stability studies indicated that the formulation was stable. The overall results of study indicated about successful development of colon targeted liquisolid formulation of xanthohumol that can be further explored for pre-clinical studies.