Design, Characterization, and In Vivo Pharmacokinetics of Tacrolimus Proliposomes

The objective of this study was to develop proliposomal formulation for a poorly bioavailable drug, tacrolimus. Proliposomes were prepared by thin film hydration method using different lipids such as hydrogenated soy phosphatidylcholine (HEPC), soy phosphatidylcholine (SPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoylphosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. Proliposomes 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 using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley (SD) rats. Among the different formulations, proliposomes with drug/DSPC/cholesterol in the ratio of 1:2:0.5 demonstrated the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes compared to pure tacrolimus in purified water after 1 h. Tacrolimus permeability across PAMPA and everted rat intestinal perfusion models was significantly higher with proliposomes. The optimized formulation of proliposomes indicated a significant improvement in the rate and absorption of tacrolimus. Following a single oral administration, a relative bioavailability of 193.33% was achieved compared to pure tacrolimus suspension.