QBD Approach for the Design, Optimization, Development, and Characterization of Naringenin-Loaded Phytosomes to Enhance Solubility and Oral Bioavailability

Abstract

Purpose

The design, optimization, preparation, and characterization of phytosomes loaded with naringenin were the goals of the current work. The present work was intended to enhance solubility and bioavailability of naringenin.

Method

The Box-Behnken design with three factors and three levels was employed to optimize the process parameters of naringenin loaded phytosomes. In the end, the design expert software’s desirability function technique helped to identify the ideal process conditions. Reproducible techniques and independent variables, including a ratio of drug: phospholipid concentration, a processing temperature, and processing time, were used to formulate the optimized batch. Using the Box-Behnken design, the influence of these independent factors on the dependent variables, such as % entrapment efficiency and % product yield, was assessed. The optimization of the formulation was also characterized by means of tests for solubility, vesicle size, zeta potential, PDI, FTIR, XRPD, DSC, SEM, TEM, in vitro release study, in vivo bioavailability study, and stability study.

Results

It was discovered that the optimized formulation had a 64.21% product yield and a 95.26% EE. The aqueous solubility of formulated naringenin phytosomes was increased from 24.65 ± 0.46 to 176.55 ± 0.25 µg/mL. The vesicle size was found to be 161.9 nm ± 5.6, and ZP and PDI was − 22.8 mV ± 0.4 and 0.444 ± 0.07, respectively. FTIR, XRPD, and DSC confirmed the formation of phytosomes. In SEM of naringenin-loaded phytosomes, significant change in morphology and shape were observed which confirmed the absence of crystallinity of naringenin. The uniform structure and spherical shape were demonstrated by TEM. The comparative in vitro drug release study of naringenin loaded phytosomes showed the sustained release characteristics of phytosomes which reached 95.26% compared to pure naringenin reached 33.76% at the end of 12 h. Following oral administration of NGNP, the concentration of NGN in rabbit plasma at various time intervals was assessed by HPLC. The pharmacokinetic characteristics of NGNP in the rabbit were T_max = 1.5 h, C_max = 2.532 0.256 µg/mL, and AUC_0-24 = 26.443 µg/mL·h.

Conclusion

Therefore, results demonstrated the importance of optimization of formulation development using quality by design strategy to achieve phytosomes with consistent quality.

Graphical Abstract