Abstract
BackgroundChrysin 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.ObjectiveThis study aimed to develop an effective oral formulation of chrysin to improve its in vivo effect as an absorption enhancer.MethodSolid 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.ResultsSDs 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 effect.ConclusionThe 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.
Highlights
Breast Cancer Resistance Protein (BCRP), an ATPBinding Cassette (ABC) transporter, involves in tumor cell resistance against diverse chemotherapeutic drugs by actively extruding the drugs from cells [1]
The solid dispersion (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
Because the solubilization of chrysin is a critical factor to ensure the adequate in vivo performance of chrysin as a breast cancer resistance protein (BCRP) inhibitor for enhancing oral absorption of BCRP substrates, SDs of chrysin were prepared with various hydrophilic carriers
Summary
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
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