Purpose

To develop microbial and pH-triggered colon-targeted budesonide pellets utilising the Quality by Design (QbD) approach. Several polysaccharide-based natural gums selected using a retrospective research strategy were screened for their efficacy in developing a microbial degradation–based colon-targeted Drug Delivery System (DDS).

Methods

The viscosity profiles were generated in the presence of a prebiotic culture medium that simulated the effect of 4% rat cecal content. Critical process parameters (CPPs) such as spheronization speed and time and formulation variables (CMAs) such as proportion of tamarind gum and microcrystalline cellulose (MCC):lactose were selected as independent variables for screening design 2⁴ FFD (full factorial design) to sort out the crucial parameters for the further optimization of pellets. The significant dependent variables were aspect ratio, particle size distribution, and % CDR (cumulative drug release) at 2 h. Pellets were super coated with the enteric polymer Eudragit S100. The screened range was further revealed to Box Behnken Design (BBD) for response surface optimization.

Results

On the basis of viscometric analysis, tamarind gum was selected for formulation development. Based on the screening design, considering the constraints of aspect ratio, particle size distribution, and % CDR at 2 h in the range of 1–1.2, 1–1.3, and < 25%, respectively, the independent variables selected for Box Behnken Design (BBD) were proportion of gum and % MCC in the ranges of 2–3 g and 30–40%, respectively. The optimization design space was generated based on the criteria of LT 10% of the drug in the first 5 h and MT 80% in the first 9 h to achieve colon targeting.

Conclusion

Tamarind gum is efficient for colon targeting, and its proportion of 2.5–3 g along with an enteric coating of 6% leads to an optimised formulation.

中文翻译：

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使用 QbD 方法制造基于天然树胶的双触发布地奈德多颗粒结肠靶向给药系统

目的

利用质量源于设计 (QbD) 方法开发微生物和 pH 触发的结肠靶向布地奈德微丸。使用回顾性研究策略选择的几种基于多糖的天然树胶在开发基于微生物降解的结肠靶向药物输送系统（DDS）方面的功效进行了筛选。

方法

粘度曲线是在存在益生元培养基的情况下生成的，该培养基模拟了 4% 大鼠盲肠含量的影响。^{选择关键工艺参数（CPP）（例如滚圆速度和时间）以及配方变量（CMA）（例如罗望子胶和微晶纤维素（MCC）：乳糖的比例）作为筛选设计2 4} FFD（全析因设计）进行排序的自变量找出进一步优化颗粒的关键参数。重要的因变量是纵横比、粒径分布和 2 小时时的 % CDR（累积药物释放）。丸剂用肠溶聚合物 Eudragit S100 进行超级包衣。筛选的范围进一步透露给 Box Behnken Design (BBD) 以进行响应面优化。

结果

在粘度分析的基础上，选择罗望子胶进行配方开发。根据筛选设计，考虑长径比、粒径分布和 2 h % CDR 分别在 1-1.2、1-1.3 和 < 25% 范围内的约束，为 Box Behnken Design 选择的自变量(BBD) 分别为 2-3 g 和 30-40% 范围内的口香糖比例和 % MCC。根据前5小时LT 10%、前9小时MT 80%的标准生成优化设计空间，以实现结肠靶向。

结论

罗望子胶可有效靶向结肠，其 2.5-3 g 的比例以及 6% 的肠溶衣形成了优化的配方。