Preparation, characterization and in vitro/vivo evaluation of tectorigenin solid dispersion with improved dissolution and bioavailability

• Published in: European journal of drug metabolism and pharmacokinetics 2016-08, Vol.41 (4), p.413-422
• Main Authors: Shuai, Shuping, Yue, Shanlan, Huang, Qingting, Wang, Wei, Yang, Junyi, Lan, Ke, Ye, Liming
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological Availability; Biomedical and Life Sciences; Biomedicine; Calorimetry, Differential Scanning - methods; Chemistry, Pharmaceutical - methods; Drug Carriers - chemistry; Drug Compounding - methods; Excipients - chemistry; Human Physiology; Isoflavones - chemistry; Isoflavones - metabolism; Male; Medical Biochemistry; Microscopy, Electron, Scanning - methods; Original Paper; Particle Size; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Povidone - chemistry; Rats; Rats, Sprague-Dawley; Solubility; Spectroscopy, Fourier Transform Infrared - methods; X-Ray Diffraction - methods
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-015-0265-6

The purpose of this study was to develop and evaluate a novel amorphous solid dispersion system for tectorigenin (TG). TG is one of isoflavone aglycones extracted from Iris tectorum and flowers of Pueraria thunbergiana , but its poor water solubility and low membrane permeability have severely restricted the clinical application. To increase the aqueous solubility and oral bioavailability of TG, we prepared the solid dispersions of tectorigenin (TG-SD) using a simple solvent evaporation process with TG, polyvinylpyrrolidone (PVP) and PEG4000 at weight ratio of 7:54:9 after tested in several ratios. The prepared solid dispersions of tectorigenin are duly characterized for drug morphological conversion, in vitro dissolution and in vivo bioavailability. The X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) studies have indicated the morphological conversion of tectorigenin to amorphous form. In vitro release profiles revealed that the % release of TG-SD was achieved 4.35-fold higher than that of the pure drug after 150 min. The oral bioavailability of the solid dispersion in rats was also increased based on AUC 0–t and C max of TG-SD, which were 4.8- and 13.1-fold higher than that of TG crystal, respectively. It is worth noting that physical mixture containing TG, PEG 4000 and PVP produced a similar level of oral exposure as TG-SD, suggesting that PEG 4000 and PVP were able to enhance bioavailability of TG in rats. However, with the reduction of particle size, TG-SD provided the fastest oral absorption compared to physical mixture and pure drug. These results demonstrated that the efficacy of solid dispersions for the enhancement of TG oral bioavailability was by increasing its aqueous solubility and the solid dispersion formulation could be a viable option for enhancing the oral bioavailability of TG.