Comparative evaluation of proliposomes and self micro-emulsifying drug delivery system for improved oral bioavailability of nisoldipine

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• 作者：Vijaykumar Nekkanti^a ; ^b ; ^{vnekkanti@westernu.edu" class="auth_mail" title="E-mail the corresponding author} ; Javier Rueda^b ; Zhijun Wang^b ; Guru V. Betageri^a ; ^b
• 关键词：Nisoldipine (PubChem CID ; 4499) ; Cholesterol (PubChem CID ; 5997) ; Tween 80 (PubChem CID ; 5284448) ; Cremophore EL (PubChem CID ; 5849927) ; Methyl cellulose (PubChem CID ; 44263857) ; Avicel (PubChem CID ; 71306959) ; DSPC (PubChem CID ; 94190) ; DMPC (PubChem CID ; 5459377) ; DMPG (PubChem CID ; 3246995) ; Dodecane (PubChem CID ; 8182)
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 May 2016
• 年：2016
• 卷：505
• 期：1-2
• 页码：79-88
• 全文大小：1638 K

文摘

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 1 h. 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.