title: Pharmacokinetic Evaluation of Improved Oral Bioavailability of Valsartan: Proliposomes Versus Self-Nanoemulsifying Drug Delivery System.
abstract: The objective of this study was to develop proliposomes and self-nanoemulsifying drug delivery system (SNEDDS) for a poorly bioavailable drug, valsartan, and to compare their in vivo pharmacokinetics. Proliposomes were prepared by thin-film hydration method using different lipids such as soy phosphatidylcholine (SPC), hydrogenated soy phosphatidylcholine (HSPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoyl phosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. SNEDDS formulations were prepared using varying concentrations of capmul MCM, labrafil M 2125, and Tween 80. Both proliposomes and SNEDDS were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water and 0.1 N HCl using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal permeation techniques. Among the formulations, the proliposomes with drug/DMPG/cholesterol in the ratio of 1:1:0.5 and SNEDDS with capmul MCM (16.0% w/w), labrafil M 2125 (64.0% w/w), and Tween 80 (18.0% w/w) showed the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SNEDDS as compared to pure valsartan. Valsartan permeability across PAMPA and everted rat intestinal permeation models was significantly higher with proliposomes and SNEDDS. Following single oral administration of proliposomes and SNEDDS, a relative bioavailability of 202.36 and 196.87%, respectively, was achieved compared to pure valsartan suspension. The study results indicated that both proliposomes and SNEDDS formulations are comparable in improving the oral bioavailability of valsartan.
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, 309 E. Second Street, Pomona, California, 91766, USA. vnekkanti@westernu.edu.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Nekkanti
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, 309 E. Second Street, Pomona, California, 91766, USA.|College of Pharmacy, Western University of Health Sciences, Pomona, California, USA.
authors.forename: Guru V
authors.initials: GV
authors.lastname: Betageri
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000068756:Valsartan / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D008081:Liposomes; D011136:Polysorbates; D000068756:Valsartan
keywords: SNEDDS; oral bioavailability; pharmacokinetics; proliposomes; valsartan