Objectives

The aim of this study was to develop and optimize the production of upadacitinib extended-release tablets containing biosynthesized hydrophilic carriers and/or polymers in the core and coating. This was achieved by applying quality by design (QbD) approach and its built-in quality control aspects to adhere to the general principles of sustainability including subsistence, efficiency, and consistency during the product life cycle. Upadacitinib is an inhibitor of the Janus kinase class of enzymes. In this study, the characterization of the reference product, physicochemical parameters of the drug molecule, and the quality target product profile was considered along with critical attributes of quality to initiate drug development. Critical attributes related to material properties, process parameters, and the formulation variables were identified, and their preliminary level of risk was assessed. The factorial design of an experiment with three center points was achieved using Design Expert v12 to investigate the customary monolithic extended-release tablets of matrix formulation. In order to evaluate tablet performance, critical quality attributes (CQAs) were determined by dissolution tests. Finally, factors that can influence the formulation, including its compositions, manufacturing procedures, and analytical evaluation, were examined. The goal was to identify formulations that exhibit a similar release pattern through the entire 12-h dissolution testing period.

Materials and Methods

Various release rates of biosynthesized polymer-based upadacitinib extended-release formulations were compared to the reference product, Innovator (Rinvoq), using in vitro dissolution test. The selected “T-5” formulation was optimized and evaluated using the QbD method to satisfy the principles of sustainability throughout the product life cycle.

Results

All experimental upadacitinib tablet formulations demonstrated favorable drug release patterns, though not to the required extent. However, the “T-5” formulation released 80% of the drug within the required time.

Conclusions

The “T-5” formulation was considered suitable for the further development of extended-release tablets of upadacitinib, as it contained optimal amount of biosynthesized hydrophilic polymer.

中文翻译：

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利用质量源于设计来开发和评估含有生物合成聚合物的乌帕替尼缓释片剂

目标

本研究的目的是开发和优化在核心和包衣中含有生物合成亲水性载体和/或聚合物的 upadacitinib 缓释片的生产。这是通过应用质量源于设计 (QbD) 方法及其内置的质量控制方面来实现的，以遵守可持续性的一般原则，包括产品生命周期中的生存、效率和一致性。Upadacitinib 是 Janus 激酶类酶的抑制剂。在这项研究中，考虑了参考产品的表征、药物分子的理化参数和目标产品质量概况以及启动药物开发的关键质量属性。确定了与材料特性、工艺参数和配方变量相关的关键属性，并对他们的初步风险水平进行了评估。使用 Design Expert v12 实现了具有三个中心点的实验的因子设计，以研究骨架配方的常规整体缓释片。为了评估片剂性能，通过溶出测试确定关键质量属性 (CQA)。最后，研究了可能影响配方的因素，包括其成分、制造程序和分析评估。目标是确定在整个 12 小时溶出测试期间表现出类似释放模式的制剂。使用 Design Expert v12 实现了具有三个中心点的实验的因子设计，以研究骨架配方的常规整体缓释片。为了评估片剂性能，通过溶出测试确定关键质量属性 (CQA)。最后，研究了可能影响配方的因素，包括其成分、制造程序和分析评估。目标是确定在整个 12 小时溶出测试期间表现出类似释放模式的制剂。使用 Design Expert v12 实现了具有三个中心点的实验的因子设计，以研究骨架配方的常规整体缓释片。为了评估片剂性能，通过溶出测试确定关键质量属性 (CQA)。最后，研究了可能影响配方的因素，包括其成分、制造程序和分析评估。目标是确定在整个 12 小时溶出测试期间表现出类似释放模式的制剂。

材料和方法

使用体外溶出测试，将基于生物合成聚合物的 upadacitinib 缓释制剂的各种释放速率与参考产品 Innovator (Rinvoq) 进行比较。所选的“T-5”配方使用QbD方法进行优化和评估，以满足整个产品生命周期的可持续性原则。

结果

所有实验性乌帕替尼片剂配方均表现出良好的药物释放模式，但未达到所需的程度。然而，“T-5”制剂在要求的时间内释放了80%的药物。

结论

“T-5”配方被认为适合进一步开发upadacitinib缓释片，因为它含有最佳量的生物合成亲水性聚合物。