International Journal of Pharmaceutics 415 (2011) 89–94 Contents lists available at ScienceDirect International Journal of Pharmaceutics jo ur nal homep a ge: www.elsevier.com/locate/ijpharm Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: In vitro and in vivo evaluation Hyo-Kyung Han a,∗ , Beom-Jin Lee b , Hyoung-Kyu Lee c a College of Pharmacy, Dongguk University-Seoul, Pil-dong-3-ga, Jung-gu, Seoul 100-715, Republic of Korea b Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea c BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea a r t i c l e i n f o Article history: Received 25 January 2011 Received in revised form 20 April 2011 Accepted 20 May 2011 Available online 27 May 2011 Keywords: Biochanin A Solid dispersion Dissolution Bioavailability a b s t r a c t 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. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Biochanin A (5,7-dihydroxy-4 ′ -methoxy-isoflavone) is one of the major isoflavones found in red clover and certain herbal prod- ucts, which are marketed for the treatment of post-menopausal symptoms including hot flashes and osteoporosis (Atkinson et al., 2004; Booth et al., 2006; Coon et al., 2007; Risbridger et al., 2001). In addition, biochanin A has various biological activities such as antioxidant, anti-inflammatory, antiviral and anti-carcinogenic effects (Puli et al., 2006). Biochanin A is also known as an inhibitor of P-glycoprotein (P-gp), a major efflux transporter protein (Zhang and Morris, 2003). As P-gp is widely expressed in intestine, liver, blood–brain barrier and kidney, it has a great impact on the absorption, distribution and elimination of various therapeutic compounds including taxol, vinca alkaloids and anthracyclines (Ambudkar et al., 1999; Germann, 1996). Therefore, biochanin A has gained great attention as a potential absorption enhancer for P-gp substrates, based on its strong inhibition effect on P-gp activ- ity in the cell culture systems. However, in contrast to the in vitro results, the oral administration of biochanin A did not improve the bioavailability of P-gp substrates such as doxorubicin, cyclosporine ∗ Corresponding author. Tel.: +82 2 2260 3957. E-mail address: hkhan@dongguk.edu (H.-K. Han). A and paclitaxel in rats even at the high dose (250 mg/kg) (Zhang et al., 2010). This discrepancy between in vitro and in vivo results could be explained by the poor bioavailability of biochanin A. The oral bioavailability of biochanin A is very low (1–2%) that might be related to, at least in part, its low aqueous solubility (Moon et al., 2006). Therefore, improving the solubility and bioavailability of biochanin A should be critical to maximize its utility as a P-gp inhibitor. Solid dispersion with hydrophilic carriers has been demon- strated as a promising technique for improving the solubility and dissolution rate of poorly water soluble drugs (Vasconcelos et al., 2007). For example, gelucire-based solid dispersion of ritonavir markedly increased the solubility and dissolution of ritonavir, resulting in the enhanced oral exposure of ritonavir (Sinha et al., 2010). Also, the solid dispersion formulation of ibuprofen using poloxamer 407 was effective to improve the dissolution and oral bioavailability of ibuprofen (Newa et al., 2008). Rajebahadur et al. (2006) also have reported that the solubility and dissolution rate of nifedipine were significantly enhanced by the solid dispersion preparation with Solutol ® HS15. The improved solubility and dis- solution by using solid dispersion formulation could be explained by the particle size reduction, the change of drug crystallinity to amorphous form, the solubilizing effect of hydrophilic carriers and better wettability of drugs surrounded by carriers (Ahuja et al., 2007; Vasconcelos et al., 2007). Therefore, the present study 0378-5173/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2011.05.055