A novel nanosized phospholipid complex of Biochanin A for improving oral bioavailability: Preparation and in-vitro/in-vivo characterizations

Abstract

Biochanin A (BCA) is a natural methoxylated-isoflavone and has been stated to have various therapeutic potentials. However, poor aqueous solubility and low oral bioavailability circumscribed its usage as a therapeutic molecule. Therefore, nano-sized BCA-phospholipid complex (nBCA-PLCs) was developed using solvent evaporation and ultra-sonication method to enhance the poor aqueous solubility and low oral bioavailability of BCA. The optimized nBCA-PLCs showed monodisperse spherical particles with a mean diameter of 329.63 ± 35.71 nm (PDI 0.288 ± 0.03), the zeta potential of (−) 53.9 ± 1.24 mV and drug entrapment efficiency of about 94.62 ± 4.19%. In vitro release study revealed that more than 99% drug was released from developed nBCA-PLCs. The formation of nBCA-PLCs complex and the loss of a crystalline state of BCA in the developed formulation were confirmed by solid-state characterizations including DSC, FTIR, and powder XRD. In situ single-pass intestinal permeability (SPIP) study showed a significant increase (2.04 fold) in the effective intestinal permeability (Peff) of BCA from nBCA-PLCs as compared with plain BCA suspension. Similarly, the oral administration of BCA-PLCs and nBCA-PLCs in Sprague Dawley (SD) rats showed 2.4-fold and 7.2 fold increase in relative bioavailability of BCA from BCA-PLCs and nBCA-PLCs, respectively as compared with plain BCA suspension. Thus, the developed nBCA-PLCs can be promising to overcome the poor aqueous solubility and increase the oral bioavailability of this poorly aqueous soluble molecule.