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

Schütt, M. and Stamatopoulos, K. and Batchelor, H.K. and Simmons, M.J.H. and Alexiadis, A. (2022) 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. European Journal of Pharmaceutical Sciences, 179. 106310. ISSN 0928-0987 (https://doi.org/10.1016/j.ejps.2022.106310)

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Abstract

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.

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