Enhanced Oral Bioavailability of Pueraria Flavones by a Novel Solid Self-microemulsifying Drug Delivery System (SMEDDS) Dropping Pills

Abstract

To improve bioavailability of pueraria flavones (PF), a self-microemulsifying drug delivery system (SMEDDS) dropping pills composed of PF, Crodamol GTCC, Maisine 35-1, Cremophor RH 40, 1,2-propylene glycol and polyethylene glycol 6000 (PEG6000) was developed. Particle size, zeta potential, morphology and in vitro drug release were investigated, respectively. Pharmacokinetics, bioavailability of PF-SMEDDS dropping pills and commercial Yufengningxin dropping pills were also evaluated and compared in rats. Puerarin treated as the representative component of PF was analyzed. Dynamic light scattering showed the ability of PF-SMEDDS dropping pills to form a nanoemulsion droplet size in aqueous media. The type of media showed no significant effects on the release rate of PF. PF-SMEDDS dropping pills were able to improve the in vitro release rate of PF, and the in vitro release of these dropping pills was significantly faster than that of Yufengningxin dropping pills. There was a dramatic difference between the mean value of t 1/2, peak concentration (C max ), the area of concentration-time curve from 0 to 6 h (AUC 0-6 h ) of PF-SMEDDS dropping pills and that of commercial Yufengningxin dropping pills. A pharmacokinetic study showed that the bioavailability of PF was greatly enhanced by PF-SMEDDS dropping pills. The value of C max and relative bioavailability of PF-SMEDDS dropping pills were dramatically improved by an average of 1.69-and 2.36-fold compared with that of Yufengningxin dropping pills after gavage administration, respectively. It was concluded that bioavailability of PF was greatly improved and that PF-SMEDDS dropping pills might be an encouraging strategy to enhance the oral bioavailability of PF.Key words self-microemulsion; pueraria flavone (PF); dropping pill; release in vitro; relative bioavailability Radix Puerariae, the dried root of the leguminous plant pueraria lobata (WILLD.) OHWI, is a traditional Chinese herb medicine. Pueraria flavones (PF), major active ingredients extract from pueraria, are mixtures of several active ingredients that include puerarin, daidzin, daidzein, puerarin-7-xyloside and so on. Puerarin is the most abundant and major active ingredient. PF were found effective clinically to treat a variety of cardiovascular diseases, 1) including coronary heart disease, angina pectoris and hypertension. It was also effective in treating arrhythmia, migraines, sudden deafness and menopause, etc. 2,3)However, the effectiveness of PF as cardiovascular disease remedy is restricted by its poor solubility, short elimination half-life and rapid first-pass metabolism after oral administration. Only 15.91% of PF are absorbed from the gastrointestinal tract after oral administration.4) The commercial formulations of PF include dropping pills, tablets and injection. Only 3.95% of puerarin in Yufengningxin tablets is absorbed compared with puerarin injection. 5) Yufengningxin dropping pills are a formulation of PF obtained from pueraria lobata and are marketed in China. In order to improve the bioa...

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