title: Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation.
abstract: The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol HS15 and HPMC 2910. Solubility of biochanin A was enhanced by 8-60 folds as the drug-carrier ratio was increased in SDs. Furthermore, compared to pure biochanin A or physical mixture (PM), SDs significantly improved the dissolution rate and the extent of drug release. Particularly, SDs (Drug:Solutol HS15:HPMC 2910=1:5:5 or 1:10:10) achieved the rapid and complete drug release (approximately 100% within 1h) at pH 6.8. The XRD patterns indicated that SDs might enhance the solubility of biochanin A by changing the drug crystallinity to amorphous state in addition to the solubilizing effect of hydrophilic carriers. The improved dissolution of biochanin A via SD formulation appeared to be well correlated with the enhanced oral exposure of biochanin A in rats. After an oral administration of SD (Drug:Solutol HS15:HPMC 2910=1:10:10), C(max) and AUC of biochanin A were increased by approximately 13 and 5 folds, respectively, implying that SDs could be effective to improve the bioavailability of biochanin A. In conclusion, solid dispersion with Solutol HS15 and HPMC 2910 appeared to be promising to improve the dissolution and oral exposure of biochanin A.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Pil-dong-3-ga, Jung-gu, Seoul 100-715, Republic of Korea. hkhan@dongguk.edu
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
authors.forename: Hyoung-Kyu
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D019833:Genistein / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D048789:Phytoestrogens / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D048789:Phytoestrogens; D019833:Genistein; C004541:biochanin A