ABSTRACT
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.
Subject(s)
Animals , Dogs , Male , Administration, Oral , Area Under Curve , Biological Availability , Drug Compounding , Drug Delivery Systems , Methods , Emulsifying Agents , Chemistry , Emulsions , Isoflavones , Blood , Chemistry , Pharmacokinetics , Oleic Acid , Chemistry , Particle Size , Polysorbates , Chemistry , Propylene Glycols , Chemistry , Solubility , Surface-Active Agents , Chemistry , Vasodilator Agents , Blood , Chemistry , PharmacokineticsABSTRACT
<p><b>AIM</b>To evaluate the self-emulsifying ability and dissolution behavior of tretinoin in vitro and the pharmacokinetic behavior in beagle dogs.</p><p><b>METHODS</b>The self-emulsifying rate was evaluated by determining the intensity of scattered light at different time and the particle size of resultant emulsions after self-emulsifying were observed by optical microscope. The plasma concentrations were determined by HPLC and dissolution and pharmacokinetic behavior of self-emulsifying formulations were evaluated by comparison with commercial capsules.</p><p><b>RESULTS</b>The area under the curve (AUC) was significantly higher in the tretinoin self-emulsifying formulation group (3048.0 mg x h x L(-1)) than that in the commercial capsule group (1826.0 mg x h x L(-1)). Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%).</p><p><b>CONCLUSION</b>The self-emulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.</p>