Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: In vitro and in vivo evaluation

• Published in: International journal of pharmaceutics 2011-08, Vol.415 (1), p.89-94
• Main Authors: Han, Hyo-Kyung, Lee, Beom-Jin, Lee, Hyoung-Kyu
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Bioavailability; Biochanin A; Biological and medical sciences; Biological Availability; Chromatography, High Pressure Liquid; crystal structure; Dissolution; Dose-Response Relationship, Drug; Drug Carriers - chemistry; Drug Compounding - methods; Drug Stability; drugs; General pharmacology; Genistein - administration & dosage; Genistein - chemistry; Genistein - pharmacokinetics; hydrophilicity; Hydrophobic and Hydrophilic Interactions; in vivo studies; Male; Medical sciences; oral administration; oral exposure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phytoestrogens - administration & dosage; Phytoestrogens - chemistry; Phytoestrogens - pharmacokinetics; Rats; Rats, Sprague-Dawley; Solid dispersion; Solubility; solubilization; X-Ray Diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.05.055

. The solid dispersions using the mixture of Solutol® HS15 and HPMC 2910 appeared to be effective to improve the dissolution and oral exposure of biochanin A. [Display omitted] ► SDs of biochanin A with Solutol ® HS15 and HPMC 2910 were prepared and evaluated. ► SDs achieved the rapid and complete drug release (approximately 100% within 1 h). ► SDs significantly improved the oral exposure of biochanin A in rats. 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 1 h) 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.