Development of Solid Self-Nanoemulsifying Drug Delivery System of Rhein to Improve Biopharmaceutical Performance:...

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.

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 3² factorial design. The optimized formulation was characterized for Fourier transform infrared spectroscopy, differential scanning calorimetry, powdered X-ray diffraction, and Field emission scanning electron microscopy. Further, the oral bioavailability study and brain tissue pharmacokinetics study were performed on Sprague-Dawley rats.

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 (p ≤ 0.05) value of C_max and AUC_0-t of RS-SNEDDS (8 ± 0.930 μg/mL and 37.79 ± 2.01 μg/mL*hr) compared to free rhein suspension (1.96 ± 0.712 μg/mL and 7.32 ± 0.946 μg/mL*hr) which indicated the enhancement of bioavailability of RS-SNEDDS. We also examined the C_max and AUC_0-t of RS-SNEDDS in the brain and it was found to be 2.90 ± 0.171 μg/mL and 18.18 ± 1.68 μg/mL*hr respectively.

This study concludes that the RS-SNEDDS improves brain tissue concentration and oral bioavailability, both of which increase therapeutic potential.