Development of Solid Self-Nanoemulsifying Drug Delivery System of Rhein to Improve Biopharmaceutical Performance: Physiochemical Characterization, and Pharmacokinetic Evaluation.

Introduction: Rhein, a natural bioactive lipophilic compound with numerous pharmacological activities, faces limitations in clinical application due to poor aqueous solubility and low bioavailability. Thus, this study aimed to develop a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) to improve solubility and bioavailability. Methods: The RL-SNEDDS was prepared by aqueous titration method with eucalyptus oil (oil phase), tween 80 (surfactant), and PEG 400 (co-surfactant) and optimization was performed by 3 Results: The optimized RL-SNEDDS had an average droplet size of 129.3 ±1.57 nm, zeta potential of -24.6 mV ±0.34, % transmittance of 94.82 ± 0.61, and encapsulation efficiency of 98.86 ± 0.23. Furthermore, RL-SNEDDS was transformed into solid RL-SNEDDS (RS-SNEDDS) to increase stability. In vitro release of rhein from RS-SNEDDS showed prolonged release up to 24h with 99.03± 1.04% drug release. Differential scanning calorimetry and powdered X-ray diffraction analysis confirmed the reduction in drug crystallinity and supported the results of the dissolution study. Field emission scanning electron microscopy analysis revealed the smooth and spherical nanosized globule of SNEDDS. Moreover, the in vivo pharmacokinetic study showed a significantly higher ( Conclusion: This study concludes that the RS-SNEDDS improves brain tissue concentration and oral bioavailability, both of which increase therapeutic potential.