Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, Etiler 06330, Ankara, Turkiye.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, Etiler 06330, Ankara, Turkiye; Department of Pharmaceutical Technology, Faculty of Pharmacy, Zonguldak Bulent Ecevit University, Esenkoy, 67600, Zonguldak, Turkiye.
Int J Pharm. 2023 Aug 25;643:123219. doi: 10.1016/j.ijpharm.2023.123219. Epub 2023 Jul 9.
The study reported here aimed to develop and optimize the S-SNEDDS tablet of bosentan (BOS) and to investigate its pharmacokinetic and biodistribution properties. The BOS-loaded SNEDDS have been developed and characterized in a previous study. The BOS-loaded SNEDDS formulation was converted to S-SNEDDS using Neusilin® US2. The S-SNEDDS tablets were obtained using the direct compression technique, and in vitro dissolution, in vitro lipolysis, and ex-vivo permeability studies of the tablets were performed. The S-SNEDDS tablet and reference tablet (Tracleer®) were administered to male Wistar rats at 50 mg/kg dose by oral gavage in fasted and fed state conditions. The biodistribution of the S-SNEDDS tablet was investigated in Balb/c mice using fluorescent dye. The tablets were dispersed in distilled water before administration to animals. The relationship between in vitro dissolution data and in vivo plasma concentration was examined. The S-SNEDDS tablets showed 2.47, 7.49, 3.70, and 4.39 increases in the percentages of cumulative dissolution in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively, when compared to the reference, and increased the C and AUC 2.65 and 1.28-fold and 4.73 and 2.37-fold in fasted and fed states, respectively, when compared to the reference. S-SNEDDS tablets also significantly reduced interindividual variability in both fasted and fed states (p < 0.05). The XenoLight™ DiR and VivoTag® 680XL labeled S-SNEDDS tablet formulation increased the real-time biodistribution in the body by factors of 2.4 and 3.4 and organ uptake and total emission increased by factors of 2.8 and 3.1, respectively. The IVIVR has been successfully established for S-SNEDDS tablets (R > 0.9). The present study confirms the potential of the S-SNEDDS tablet to enhance the in vitro and in vivo performance of BOS.
本研究旨在开发和优化波生坦（BOS）的 S-SNEDDS 片剂，并研究其药代动力学和生物分布特性。BOS 载 SNEDDS 已在先前的研究中进行了开发和表征。使用 Neusilin® US2 将 BOS 载 SNEDDS 制剂转化为 S-SNEDDS。使用直接压缩技术获得 S-SNEDDS 片剂，并对片剂进行体外溶出度、体外脂肪酶和离体渗透性研究。S-SNEDDS 片剂和参比片剂（Tracleer®）以 50mg/kg 剂量通过口服灌胃在禁食和进食状态下给予雄性 Wistar 大鼠。使用荧光染料在 Balb/c 小鼠中研究 S-SNEDDS 片剂的生物分布。在给予动物之前，将片剂分散在蒸馏水中。检查了体外溶出数据与体内血浆浓度之间的关系。与参比相比，S-SNEDDS 片剂在 FaSSIF、FeSSIF、FaSSIF-V2 和 FeSSIF-V2 中的累积溶出百分比分别增加了 2.47、7.49、3.70 和 4.39%，并在禁食和进食状态下分别增加了 2.65 和 1.28 倍和 4.73 和 2.37 倍与参比相比。S-SNEDDS 片剂还显著降低了禁食和进食状态下的个体间变异性（p<0.05）。XenoLight™DiR 和 VivoTag®680XL 标记的 S-SNEDDS 片剂配方分别将体内实时生物分布增加了 2.4 倍和 3.4 倍，器官摄取和总发射分别增加了 2.8 倍和 3.1 倍。已成功为 S-SNEDDS 片剂建立了 IVIVR（R>0.9）。本研究证实了 S-SNEDDS 片剂增强 BOS 体外和体内性能的潜力。
