1. Development and pharmacokinetic evaluation of Neusilin® US2-based S-SNEDDS tablets for bosentan: Fasted and fed states bioavailability, IVIS® real-time biodistribution, and ex-vivo imaging.
- Author
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Yilmaz Usta D, Olgac S, Timur B, and Teksin ZS
- Subjects
- Rats, Animals, Mice, Male, Bosentan, Tissue Distribution, Rats, Wistar, Biological Availability, Emulsions, Tablets pharmacokinetics, Solubility, Administration, Oral, Particle Size, Drug Delivery Systems methods, Nanoparticles
- Abstract
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
max 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 (R2 > 0.9). The present study confirms the potential of the S-SNEDDS tablet to enhance the in vitro and in vivo performance of BOS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Zeynep Safak Teksin reports financial support was provided by Scientific and Technological Research Council of Turkey. Zeynep Safak Teksin reports a relationship with Scientific and Technological Research Council of Turkey that includes: funding grants. Zeynep Safak Teksin has patent #TR201915787 issued to Zeynep Safak Teksin. Duygu Yilmaz Usta - Gazi University]., (Copyright © 2023 Elsevier B.V. All rights reserved.)- Published
- 2023
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