Purpose

The main objective was to develop and optimize a multiparticulate system of 5-fluorouracil through the Box–Behnken design (BBD) and desirability function and coating of the optimized batch for increased therapeutic efficacy and targeting for the treatment of colorectal cancer.

Method

It is essential to understand the factors and quality aspects involved in the formulation of a multiparticulate system through optimization. The ionotropic gel method was used to create an optimized batch, with selected independent factors such as sodium alginate, pectin concentrations, and curing time on the response variables such as particle size and entrapment efficiency of 5-fluorouracil-loaded microparticle. The relationship between the independent and dependent variables was examined by utilizing the contour, response surface designs, mathematical calculations, and desirability function produced by Design-Expert.

Result

The ionotropic gelation process was used to create an optimized batch, and the generated microparticles had a 674 µm particle size and a 90.81% drug entrapment efficiency. The observed answers were very similar with a bias of less than 5% when compared to the expected value and desirability function. A second layer of Eudragit S100 was applied to the improved formulation. The coated microbeads released pH 1.2 at a rate of less than 10%. After 10 h, more than 55.12% of the drug was released into the intestinal area (pH 6.8). The kinetics investigation demonstrated that the created formulation for the Higuchi and Korsmeyer-Peppas models possessed linearity, as shown by the plots, with R² values of 0.9887 and 0.9236, respectively. This outcome supported the formulation’s extended-release behavior.

Conclusion

It was suggested that the drugs would be delivered to the desired place using the microbeads created in this study. The developed microbeads were probably made of small particles that contained a high percent drug entrapment. According to the findings, multiparticulate can be a possible carrier for the delivery of drugs to the colon, and the Box–Behnken design and desirability function can be an active strategy for optimizing the formulation. Its cytotoxicity is maintained by being formulated as a multiparticulate, and it is also suited for administration to patients with colorectal cancer.

中文翻译：

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使用 Box-Behnken 设计和结肠靶向期望函数优化 5-氟尿嘧啶微珠的质量源于设计方法

目的

主要目标是通过 Box-Behnken 设计 (BBD) 以及优化批次的合意性函数和涂层来开发和优化 5-氟尿嘧啶多颗粒系统，以提高治疗效果并靶向治疗结直肠癌。

方法

通过优化了解多颗粒系统配方中涉及的因素和质量方面至关重要。使用离子型凝胶方法创建优化批次，并选择独立因素（例如海藻酸钠、果胶浓度和固化时间）对响应变量（例如负载 5-氟尿嘧啶的微粒的粒径和包封效率）的影响。通过利用 Design-Expert 生成的等高线、响应曲面设计、数学计算和合意性函数来检查自变量和因变量之间的关系。

结果

使用离子型凝胶化工艺来创建优化批次，生成的微粒具有 674 µm 的粒径和 90.81% 的药物包封率。与预期值和意愿函数相比，观察到的答案非常相似，偏差小于 5%。在改进的配方中应用了第二层 Eudragit S100。包被的微珠以低于 10% 的速率释放 pH 1.2。10小时后，超过55.12%的药物被释放到肠道区域（pH 6.8）。动力学研究表明，为 Higuchi 和 Korsmeyer-Peppas 模型创建的公式具有线性关系，如图所示，R ²值分别为 0.9887 和 0.9236。这一结果支持了该制剂的缓释行为。

结论

有人建议使用本研究中创建的微珠将药物输送到所需的位置。所开发的微珠可能由含有高百分比药物包封的小颗粒制成。根据研究结果，多颗粒可以成为将药物输送到结肠的可能载体，而 Box-Behnken 设计和合意性函数可以成为优化配方的积极策略。它的细胞毒性通过配制为多颗粒而得以维持，并且也适合用于结直肠癌患者。