Development of a digital twin of a tablet that mimics a real solid dosage form: Differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model
Development of a digital twin of a tablet that mimics a real solid dosage form: Differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model
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DOI：
10.1016/j.ejps.2022.106310
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发表时间：
2022-10-21
影响因子：
4.6
通讯作者：
Alexiadis, A.
中科院分区：
文献类型：
--
作者：
Schuett, M.;Stamatopoulos, K.;Alexiadis, A.
结肠靶向固体剂型的性能通常使用标准化药典溶出装置（如 USP II 或小型复制品 mini-USP II）进行评估。然而，这些方法无法复制结肠环境中的流体动力学和剪切应力，而这对于片剂的药物释放过程至关重要。在这项工作中，计算机模拟用于创建溶出度仪的数字孪生，并开发一种方法来创建表现逼真的片剂的数字孪生。这些模型用于研究 mini-USP II 和生物相关结肠模型中不同桨速作用于片剂的药物释放曲线和剪切速率，以了解如何操作 mini-USP II 来实现更真实（即体内）的流体动力学条件。片剂的行为和模拟中使用的运动模式分别源自实验和体内数据，以获得对片剂崩解/药物释放过程的深刻见解。我们建议在 mini-USP II 中使用“开关”操作模式来生成剪切速率峰值，这将更好地反映人体结肠的体内条件，而不是恒定的桨速。
The performance of colon-targeted solid dosage forms is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these fail to replicate the hydrodynamics and shear stresses in the colonic environment, which is crucial for the tablet's drug release process. In this work, computer simulations are used to create a digital twin of a dissolution apparatus and to develop a method to create a digital twin of a tablet that behaves realistically. These models are used to investigate the drug release profiles and shear rates acting on a tablet at different paddle speeds in the mini-USP II and biorelevant colon models to understand how the mini-USP II can be operated to achieve more realistic (i.e., in vivo) hydrodynamic conditions.The behaviour of the tablet and the motility patterns used in the simulations are derived from experimental and in vivo data, respectively, to obtain profound insights into the tablet's disintegration/drug release processes. We recommend an "on-off" operating mode in the mini-USP II to generate shear rate peaks, which would better reflect the in vivo conditions of the human colon instead of constant paddle speed.