Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies
Trans-resveratrol self-nano-emulsifying drug delivery system (SNEDDS) with enhanced bioavailability potential: optimization, pharmacokinetics and in situ single pass intestinal perfusion (SPIP) studies
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DOI：
10.3109/10717544.2014.885616
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发表时间：
2015-06-01
期刊：
影响因子：
6
通讯作者：
Pai, Roopa S.
中科院分区：
文献类型：
--
作者：
Singh, Gurinder;Pai, Roopa S.
反式白藜芦醇（t-RVT）是一种有效的抗氧化剂。由于广泛的全身前代谢和肝肠再循环的存在，t-RVT的生物利用度几乎为零。目前的研究旨在开发使用t-RVT的长链甘油三酯（LCT）的自纳米乳化药物递送系统（SNEDDS），以试图绕过这些障碍。平衡溶解度研究表明，选择月桂乙二醇FCC作为脂质，Labrasol和Transcutol P作为表面活性剂，用于配制SNEDDS。构建三元相图，选择纳米乳的面积，以及脂质（X-1）和表面活性剂（X-2）的量作为关键因素变量。使用3（2）中心复合设计（CCD）优化SNEDDS，并使用重叠图定位优化制剂（OPT）。纳米尺寸范围和zeta电位的高负值描述了SNEDDS的非聚结性质。优化的制剂表明相对维斯纯药物，药物释放曲线显著改善。浊点测定和加速稳定性研究确定了OPT的稳定性。K-a值（3.29倍）和AUC值（4.31倍）的增加表明与纯药物相比，OPT的生物利用度的速率和程度显着提高。Wistar大鼠原位灌注（SPIP）研究表明，SNEDDS的吸收率和渗透性参数与纯药物相比显著增强。A级体外/体内相关性的成功建立证实了体外溶出环境模拟体内条件的明智选择。因此，本研究报告成功开发了SNEDDS，显著提高了t-RVT的生物利用度。
Trans-resveratrol (t-RVT) is a potent antioxidant. By virtue of extensive pre-systemic metabolism and existence of enterohepatic recirculation, t-RVT bioavailability is almost zero. The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides (LCTs) of t-RVT in an attempt to circumvent such obstacles. Equilibrium solubility studies indicated the choice of Lauroglycol FCC as lipid, and of Labrasol and Transcutol P as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X-1) and surfactant (X-2) as the critical factor variables. The SNEDDS were optimized using 3(2) central composite design (CCD) and the optimized formulation (OPT) located using overlay plot. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the SNEDDS. Optimized formulation indicated marked improvement in drug release profile vis-a-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT. Augmentation in the values of K-a (3.29-fold) and AUC (4.31-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT compared with pure drug. In situ perfusion (SPIP) studies in Wistar rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-a-vis the pure drug. Successful establishment of level A of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The present study, therefore, reports the successful development of SNEDDS with distinctly enhanced bioavailability of t-RVT.