Enhancement of oral bioavailability of pentoxifylline by solid lipid nanoparticles.
Pentoxifylline (PTX) is a highly water-soluble, hemorheologic drug that undergoes first-pass effect with 20% bioavailability. The solid lipid nanoparticles (SLNs) of PTX were prepared to enhance its oral bioavailability by homogenization, followed by the sonification method. Seven different variables, each at two levels, were studied: lipid type, surfactant type and concentration, speed of homogenizer, acetone:dichloromethane (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 250 nm, -30.2 mV, and 70%, respectively. Among the studied factors, the lipid type, surfactant type, and percentage had a significant effect on the particle size. Zeta potential was more affected by lipid type, acetone:DCM ratio, and sonication time. Speed of homogenizer and acetone:DCM ratio had a significant effect on the EE%. The optimized SLN was prepared by 80 mg of cetyl alcohol, 10 mg of lecithin, acetone:DCM ratio (1:2), 30-second sonication, 3% Tween 20, and a mixing rate of 800 rpm. In vitro drug release lasted for about 5 hours. It was found that the relative bioavailability of PTX in SLNs was significantly increased, compared to that of the PTX solution. SLNs offer a promising approach to improve the oral bioavailability of PTX that is affected by a high first-pass effect.
Varshosaz
Jaleh
J
Department of Pharmaceutics and Pharmacology, Isfahan University of Medical Science, Iran. varshosaz@pharm.mui.ac.ir <varshosaz@pharm.mui.ac.ir>
Minayian
Mohsen
M
Moazen
Elaheh
E
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D008055:Lipids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors
D008055:Lipids; D013501:Surface-Active Agents; D010431:Pentoxifylline