Abstract
We investigated the usefulness of a suppository containing highly concentrated glycyrrhizin monoammonium (GZ-NH4) solution prepared by pretreatment with clove oil in rats. The aims of this study were to clarify membrane permeability, the bioavailability of GZ-NH4 and the extent of tissue damage. Membrane permeability was evaluated using Ussing-type diffusion chambers, bioavailability assessed through an in vivo absorption study, tissue damage evaluated through observation of hematoxylin-eosin stained tissues and an in vitro release study was carried out to select the suppository base. The formulations used were a GZ-NH4 solution prepared using phosphate buffered solution (control), GZ-NH4 containing 50% labrasol, and GZ-NH4 pretreated with 2% clove oil at 50°C and 70°C. The GZ-NH4 concentrations of all formulations were set to 50 mg/mL. With the GZ-NH4 pretreated with 2% clove oil formulations, the apparent permeability coefficients (Papp) were 1.7- and 1.9-fold higher, respectively, than that of the control formulation. When the various formulations were applied to the rat rectum at a dose of 50 mg/kg of GZ-NH4, the bioavailability of GZ-NH4 pretreated with 2% clove oil at 70°C was 25%, the highest among the four formulations. In the in vivo absorption study, no damage to the epithelial cells of the rectum was observed. These results suggest that GZ-NH4 pretreated with 2% clove oil at 70°C is the most useful formulation for rectal administration. In the in vitro release study to select suppository base, polyethyleneglycol 1000 (PEG 1000) was selected as the hydrophilic base and Witepsol H-15 as the lipophilic base. The initial release of GZ-NH4 was highest for the Witepsol H-15 suppository base. Overall, our results suggest that a lipophilic suppository containing GZ-NH4 pretreating with 2% clove oil at 70°C has the highest release and absorption rates for GZ-NH4 in rectal administration.
