Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation
Solid self-nanoemulsifying systems of olmesartan medoxomil: Formulation development, micromeritic characterization, in vitro and in vivo evaluation
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DOI：
10.1016/j.powtec.2016.02.023
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发表时间：
2016-06-01
影响因子：
5.2
通讯作者：
Singh, Bhupinder
中科院分区：
文献类型：
--
作者：
Beg, Sarwar;Katare, O. P.;Singh, Bhupinder
目前的研究需要开发和评价固体自纳米乳化给药系统（S-SNEDDS）采用多孔载体，以提高奥美沙坦酯的口服生物利用度。平衡溶解度研究和伪三元相图显示油酸，吐温40和Transcutol HP作为脂质，表面活性剂和共溶剂的液体SNEDDS（L-SNEDDS）的配方的适用性。采用最优混料设计法对L-SNEDDS的乳化时间、微球大小和体外释药性能进行了系统的优化。通过将L-SNEDDS吸附到多孔载体（即Aerosil 200、Aeroperl 300、Sylysia 550、Neusilin US 2和Fujicalin SG）上来制备S-SNEDDS制剂，并使用Kawakita、Heckel和Leuenberger图来评价油吸附趋势、微米行为、流动性和压实特性，以确定用于S-SNEDDS片剂制剂的合适固体载体。进行体外溶出研究，以比较分析S-SNEDDS制剂的药物释放行为。在所用的各种固体载体中，Neusilin US 2表现出优异的上级吸油能力、微米特性、优异的流动性和压实性。从优化的S-SNEDDS观察到药物释放速率提高了近2.6倍，随后与L-SNEDDS相比，药物释放速率没有显著差异（p > 0.05）。在Wistar大鼠体内的药代动力学研究显示，优化的S-SNEDDS维斯纯药物溶液相比，药物的C-max和AUC分别提高了232倍和3.27倍。此外，A级体外/体内相关性（IVIVC）揭示了体外溶出性能与体内性能的高度预后能力。简而言之，本研究报告成功开发了奥美沙坦酯的S-SNEDDS，作为具有明显改善的生物制药属性的有前景的制剂策略之一。(C)© 2016 Elsevier B. V.版权所有。
The current studies entail development and evaluation of solid self-nanoemulsifying drug delivery systems (S-SNEDDS) employing porous carriers for enhancing the oral bioavailability of olmesartan medoxomil. Equilibrium solubility studies and pseudoternary phase diagrams revealed suitability of oleic acid, Tween 40 and Transcutol HP as the lipid, surfactant and cosolvent for formulation of the liquid SNEDDS (L-SNEDDS). The L-SNEDDS were systematically optimized using optimal mixture design, evaluated for emulsification time, globule size and in vitro drug release. S-SNEDDS formulations were prepared by adsorbing L-SNEDDS onto the porous carriers, viz. Aerosil 200, Aeroperl 300, Sylysia 550, Neusilin US2 and Fujicalin SG, and evaluated for oil adsorption tendency, micrometric behavior, flow properties and compaction characteristics using Kawakita, Heckel and Leuenberger plots for identifying the suitable solid carrier for formulation of S-SNEDDS tablet. In vitro dissolution studies were performed for comparative analysis of the drug release behavior from the S-SNEDDS formulation. Among the various solid carriers employed, Neusilin US2 exhibited superior oil adsorbing capacity, micrometric properties, excellent flowability and compactibility. Nearly 2.6-fold improvement in the drug release rate was observed from the optimized S-SNEDDS, followed by no significant difference in the drug release rate as compared to the L-SNEDDS (p > 0.05). In vivo pharmacokinetic studies in Wistar rats revealed 232 and 3.27-fold enhancement in C-max and AUC of the drug from the optimized S-SNEDDS vis-a-vis the pure drug solution. Also, high degree of prognostic ability of in vitro dissolution performance with in vivo performance was revealed from level A in vitro/in vivo correlations (IVIVC). In a nutshell, the present studies report successful development of S-SNEDDS of olmesartan medoxomil as one of the promising formulation strategies with distinctly improved biopharmaceutical attributes. (C) 2016 Elsevier B.V. All rights reserved.