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

中文翻译：

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用于设计、优化、开发和表征柚皮素磷脂质体以增强溶解度和口服生物利用度的 QBD 方法

目的

负载柚皮素的植物体的设计、优化、制备和表征是当前工作的目标。目前的工作旨在提高柚皮素的溶解度和生物利用度。

方法

采用三因素三水平的Box-Behnken设计来优化负载柚皮素的植物体的工艺参数。最后，设计专家软件的合意性函数技术有助于确定理想的工艺条件。使用可重复的技术和自变量（包括药物：磷脂浓度的比率、加工温度和加工时间）来制定优化的批次。使用 Box-Behnken 设计，评估了这些独立因素对因变量的影响，例如％包封效率和％产品产量。还通过溶解度、囊泡大小、zeta电位、PDI、FTIR、XRPD、DSC、SEM、TEM、体外释放研究、体内生物利用度研究和稳定性研究等测试来表征制剂的优化。

结果

结果发现，优化后的配方产品收率为64.21%，EE率为95.26%。配制的柚皮素磷脂复合物的水溶解度从 24.65 ± 0.46 增加至 176.55 ± 0.25 µg/mL。囊泡大小为 161.9 nm ± 5.6，ZP 和 PDI 分别为 - 22.8 mV ± 0.4 和 0.444 ± 0.07。FTIR、XRPD 和 DSC 证实了磷脂体的形成。在负载柚皮素的磷脂体的SEM中，观察到形态和形状的显着变化，这证实了柚皮素不存在结晶性。TEM 证明了其均匀的结构和球形形状。体外比较负载柚皮素的磷脂复合物的药物释放研究表明，在12小时结束时，磷脂复合物的缓释特性达到95.26%，而纯柚皮素则达到33.76%。口服 NGNP 后，通过 HPLC 评估不同时间间隔兔血浆中 NGN 的浓度。NGNP在家兔体内的药代动力学特征为T _max  = 1.5 h，C _max  = 2.532 0.256 µg/mL，AUC _0-24  = 26.443 µg/mL·h。

结论

因此，结果证明了使用质量设计策略优化制剂开发以获得质量一致的植物体的重要性。

图形概要