Formulation optimization of self-emulsifying preparations of puerarin through self-emulsifying performances evaluation in vitro and pharmacokinetic studies in vivo.
The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising 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 particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability 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-t)). AUC(0-t) was significantly higher in formulation F2 group (5.201 +/- 0.511) ng x mL(-1) x h and formulation F3 group (5.174 +/- 0.498) ng x mL (-1) x h than that in formulation F4 group (3.013 +/- 0.623) ng x mL(-1) x h. Also, C(max) was significantly higher in formulation F2 group (1.524 +/- 0.125) ng x mL(-1) and formulation F3 group (1.513 +/- 0.157) ng x mL(-1) than that in formulation F4 group (0.939 +/- 0.089) ng x mL(-1). Further 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) for three SEDDS formulations, but not between those of F2 and F3 (P > 0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.
Quan
Dong-Qin
DQ
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. wzbqdq@sohu.com
Xu
Gui-Xia
GX
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions; D007529:Isoflavones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
D045703:Emulsifying Agents; D004655:Emulsions; D007529:Isoflavones; D011136:Polysorbates; D011409:Propylene Glycols; D013501:Surface-Active Agents; D014665:Vasodilator Agents; D019301:Oleic Acid; C033607:puerarin