title: Comparative evaluation of proliposomes and self micro-emulsifying drug delivery system for improved oral bioavailability of nisoldipine.
abstract: The objective of this study was to develop proliposomal formulation and self micro-emulsifying drug delivery system (SMEDDS) for a poorly bioavailable drug, nisoldipine 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), Dimyristoylphosphatidylcholine (DMPC) and Dimyristoyl phosphatidylglycerol sodium (DMPG), Distearyl phosphatidylcholine (DSPC), and Cholesterol in various ratios. SMEDDS formulations were prepared using varying concentrations of Capmul MCM, Labrasol, Cremophor EL and Tween 80. Both proliposomes and SMEDDS 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 rats. Among the different formulations, proliposomes with drug:DMPC:cholesterol in the ratio of 1:2:0.5 and SMEDDS with Capmul MCM (13.04% w/w), Labrasol (36.96% w/w), Cremophor EL (34.78% w/w) and Tween 80 (15.22% w/w) demonstrated the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes and SMEDDS compared to pure nisoldipine in purified water after 1h. Nisoldipine permeability across PAMPA and everted rat intestinal perfusion models was significantly higher with proliposomes and SMEDDS. Following single oral administration of proliposomes and SMEDDS, a relative bioavailability of 301.11% and 239.87% respectively, was achieved compared to pure nisoldipine suspension.
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA; College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA. Electronic address: vnekkanti@westernu.edu.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Nekkanti
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Rueda
authors.affiliation: College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA; College of Pharmacy, Western University of Health Sciences, Pomona, CA, 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; D065546:Drug Liberation; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D015737:Nisoldipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D008055:Lipids; D008081:Liposomes; D015737:Nisoldipine
keywords: Avicel (PubChem CID: 71306959); Bioavailability; Cholesterol (PubChem CID: 5997); Cremophore EL (PubChem CID: 5849927); DMPC (PubChem CID: 5459377); DMPG (PubChem CID: 3246995); DSPC (PubChem CID: 94190); Dodecane (PubChem CID: 8182); Everted rat intestine; Methyl cellulose (PubChem CID: 44263857); Nisoldipine; Nisoldipine (PubChem CID: 4499); Pharmacokinetics; Proliposomes; SMEDDS; Tween 80 (PubChem CID: 5284448)