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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 (R 2  > 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.)

This study aimed to develop and optimize a self-nanoemulsifying drug delivery system (SNEDDS) of bosentan (BOS) to solve its poor oral bioavailability due to low water solubility. A pseudo-ternary phase diagram was created based on the solubility and emulsification studies. The major components of the formulation were selected as glyceryl monolinoleate (lipid), polyoxyl 40 hydrogenated castor oil (surfactant), and caprylocaproyl polyoxyl-8 glycerides (co-surfactant). The composition of BOS-SNEDDS was optimized using the Box-Behnken design (BBD) and then was characterized for various physicochemical properties. The in vitro dissolution, in vitro lipolysis, and ex-vivo permeability studies were performed and compared to SNEDDS and reference tablets. The fasted and fed state bioavailability of BOS-loaded SNEDDS was evaluated in Wistar rats (n = 6) compared to the reference. The prepared SNEDDS were thermodynamically stable with a droplet size of 17.11 nm, a polydispersity index of 0.180, and an emulsification time of <1 min. The BOS-loaded SNEDDS showed 3.0, 7.97, 4.23, and 4.94-fold increases in the percentages of cumulative dissolution compared to reference tablets in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively. The permeation study showed that the SNEDDS increased the drug permeation by 3.36, 19.2, 16.4, and 16.6-fold in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively. The enhancement of in vitro dissolution, in vitro lipolysis, and ex-vivo permeability was found significant (p < 0.05). SNEDDS was increased the C max and AUC 1.67 and 2.12-fold and 5.15 and 1.84-fold in fasted and fed state compared to the reference, respectively. The in vitro-in vivo relationship has been successfully performed for SNEDDS. These results indicated that the SNEDDS formulation could be a promising delivery system that enhances the absorption and oral bioavailability of BOS., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The objective of this study was to prepare ritonavir (RTV) nanosuspensions, an anti-HIV protease inhibitor, to solve its poor water solubility issues. The microfluidization method with a pre-treatment step was used to obtain the nanosuspensions. Design of Experiment (DoE) approach was performed in order to understand the effect of the critical formulation parameters which were selected as polymer type (HPMC or PVP), RTV to polymer ratio, and number of passes. Interactions between the formulation variables were evaluated according to Univariate ANOVA. Particle size, particle size distribution and zeta potential were selected as dependent variables. Scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry were performed for the in vitro characterization after lyophilization of the optimum nanosuspension formulation. The saturation solubility was examined in comparison with coarse powder, physical mixture and nanosuspension. In vitro dissolution studies were conducted using polyoxyethylene 10 lauryl ether (POE10LE) and biorelevant media (FaSSIF and FeSSIF). The results showed nanosuspensions were partially amorphous and spherically shaped with particle sizes ranging from 400 to 600nm. Moreover, 0.1-0.4 particle size distribution and about -20mV zeta potential values were obtained. The nanosuspension showed a significantly increased solubility when compared to coarse powder (3.5 fold). Coarse powder, physical mixture, nanosuspension and commercial product dissolved completely in POE10LE; however, cumulative dissolved values reached ~20% in FaSSIF for the commercial product and nanosuspension. The nanosuspension showed more than 90% drug dissolved in FeSSIF compared to the commercial product which showed ~50% in the same medium. It was determined that RTV dissolution was increased by nanosuspension formulation. We concluded that DoE approach is useful to develop nanosuspension formulation to improve solubility and dissolution rate of RTV., (Copyright © 2016 Elsevier B.V. All rights reserved.)