Background: Chrysin is a strong inhibitor of breast cancer resistance protein (BCRP) but it
is practically insoluble in water. Effective solubilization of chrysin is critical for its pharmaceutical
application as an absorption enhancer via inhibition of BCRP-mediated drug efflux.
Objective: This study aimed to develop an effective oral formulation of chrysin to improve its in vivo
effect as an absorption enhancer.
Method: Solid dispersions (SDs) of chrysin were prepared with hydrophilic carriers having surface
acting properties and a pH modulator. In vitro and in vivo characterizations were performed to select
the optimal SDs of chrysin.
Results: SDs with Brij®L4 and aminoclay was most effective in increasing the solubility of chrysin by
13-53 fold at varying drug-carrier ratios. Furthermore, SDs significantly improved the dissolution rate
and extent of drug release. SDs (chrysin: Brij®L4: aminoclay=1:3:5) achieved approximately 60% and
83% drug release within 1 h and 8 h, respectively, in aqueous medium, while the dissolution of the
untreated chrysin was less than 13%. XRD patterns indicated the amorphous state of chrysin in SDs.
The SD formulation was effective in improving the bioavailability of topotecan, a BCRP substrate in
rats. Following oral administration of topotecan with the SDs of chrysin, the Cmax and AUC of topotecan
was enhanced by approximately 2.6- and 2-fold, respectively, while the untreated chrysin had no
Conclusion: The SD formulation of chrysin with Brij®L4 and aminoclay appeared to be promising in
improving the dissolution of chrysin and enhancing its in vivo effect as an absorption enhancer.