Solid Lipid Nanoparticles for Enhancing Oral Bioavailability of Pentoxifylline

Pentoxifylline (PTX) is a highly water soluble, hemorrheologic drug that undergoes first-pass effect with 20% bioavailability. The solid lipid nanoparticles (SLNs) of PTX were prepared to enhance its oral bioavailability by a novel method according to sonification followed by homogenization. Seven different variables each at 2 levels were studied: lipid type, surfactant type and concentration, speed of homogenizer, aceton/dichloromethan (DCM) ratio, lecithin/lipid ratio and sonication time. The mean particle size and size distribution, drug entrapment efficiency (EE%), zeta potential, and drug release of the SLNs were investigated. A pharmacokinetic study was conducted in male Wistar rats after oral administration of 10 mg kg− 1 PTX in the form of free drug or SLNs. The z-average particle size, zeta potential, and EE% of the SLNs were at least 250nm, -30.2 mV and 70%, respectively. Among the studied factors the lipid type, surfactant type and percentage, had significant effect on the particle size. Zeta potential was more affected by the lipid type, acetone/DCM ratio and sonication time. Speed of homogenizer and acetone/DCM ratio had significant effect on the EE%. The optimized SLN was prepared by 80mg cetyl alcohol, 10mg lecithin, aceton/DCM ratio 1/2, 30 sec sonication, 3% Tween 20 and mixing rate of 800rpm. In vitro drug release lasted for about 5 hrs. It was found that the relative bioavailability of PTX in SLNs was significantly increased (about 5-fold) compared to that of the PTX solution in male Wistar rats. SLNs offer a new approach to improve the oral bioavailability of drugs with high first pass effect.

کلیدواژه ها:

Pentoxifylline ، Solid lipid nanoparticles ، First pass metabolism ، Enhanced bioavailability