Formulation development and pharmacokinetics of puerarin self-emulsifying drug delivery systems.
The main purpose of this work was to prepare a self-emulsifying drug delivery system (SEDDS) for a poorly water-soluble drug, puerarin. The solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided relatively higher solubility. The addition of propylene glycol as a cosurfactant improved the solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures composed of oleic acid, propylene glycol, and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region, and the particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations were investigated in beagle dogs. The bioavailability of puerarin was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and total area under the plasma concentration-time curve (AUC(0-infinity)). The analysis of the data showed a statistically significant difference between F2 and F4 (P < 0.01) as well as F3 and F4 (P < 0.01) with regard to the values of AUC(0-infinity) and C(max) but not between those of F2 and F3 (P > 0.05). In the case of parameter T(max), ke, no statistically significant difference (P > 0.05) among the values were observed. From these studies, a SEDDS containing oleic acid (17.5%), Tween 80 (34.5%), and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation for puerarin. The data suggest the potential use of SEDDS to improve the oral absorption of puerarin.
Dong-Qin
Quan
Q
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. wzbqdq@sohu.com
Gui-Xia
Xu
X
Xiang-Gen
Wu
W
D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions; D007529:Isoflavones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014665:Vasodilator Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D045703:Emulsifying Agents; D004655:Emulsions; D007529:Isoflavones; D012997:Solvents; D014665:Vasodilator Agents; C033607:puerarin