The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests, in vitro dissolution, particle size, and zeta potential were executed to optimize the formulations. The optimized formulation, that composed of Capryol 90:Tween 20:PEG 300 (5:45:50), increased RIVA solubility (285.7-fold than water), it formed nanoemulsion with a particle size of 16.15 nm, PDI of 0.25 and zeta potential of −21.8. It released 100.83 ± 2.78% of RIVA after 5 min. SNEDDS was robust to dilution with oral and parenteral fluids and showed safety to human RBCs. SNEDDS showed enhanced bioavailability after oral and intravenous administration than the oral drug suspension (by 1.25 and 1.26-fold, respectively). Moreover, it exhibited enhanced anticoagulant efficacy in the prevention and treatment of carrageenan-induced thrombosis rat model.

Objective: The aim of this work is to investigate the influence of different casting solvents on the physicochemical properties of cetylpyridinium chloride (CPC) chitosan mucoadhesive buccal films.Methods: Screening formulations were prepared by casting solvent technique using organic acids; 1% acetic acid (AA), 1% lactic acid (LA) and inorganic acid; 0.1N HCl (FS1-FS3). Then, 21X31 factorial design study was done using 2 factors; solvent type (AA, LA, Mixture of 0.1N HCl and LA) and solvent concentration (AA and LA; 1%, 2% and mixture of 0.1N HCl: 1% LA; 2:1, 1:2). Films were evaluated for their physicochemical properties through, mechanical properties, mucoadhesion, in vitro release of CPC and antimicrobial activity.Results: The studied factors showed a significant effect on both mucoadhesion and tensile strength. Film casted from 0.1 N HCl was brittle and did not show any elasticity, so it was used in further studies mixed with LA to improve physicochemical properties of the prepared films. Films casted from LA showed swelling for an initial period of 15 min then no more swelling occurred while swelling of those casted from AA occurred throughout approximately 2 h. A film containing 2:1 HCl: LA (F5) dissolved in both media while 1:2 HCl: LA (F6) showed swelling properties. This was reflected on the in vitro release of CPC in which F5 gave higher % released (DE300 min 54.37%) than the other formulations.Conclusion: Casting solvent was proved to have a significant effect on the physicochemical properties of chitosan CPC mucoadhesive films.