**Category: **Formulation and Quality

Tue, Nov 5

10:30 AM – 11:30 AM

** Purpose: **As the most widely used oral dosage form, tablets are widely manufactured, tested, and regulated. The disintegration of a tablet and, subsequently, release kinetics of the active pharmaceutical ingredient (API), is facilitated by utilizing swelling polymers and/or polysaccharides as disintegrants. The disintegration process governs the drug release kinetics, playing a key role in determining drug dissolution and eventual absorption and bioavailability. It is thus of great importance to fully understand and predict the disintegration and dissolution processes, enabling the rational design of tablet formulation. Current computational methods [1,2], nonetheless, neglect the fluid dynamics around the tablet (for example, in a testing device or even in the gastrointestinal tract) and, more importantly, fail to realistically model the mutual influence between the fluid and drug/excipient particles. Herein, we aim to develop a high-fidelity, physics-based simulation method of tablet disintegration and dissolution. We have developed a computational platform which can simulate three basic processes of tablet dissolution, including fluid-solid interaction, particle disintegration, and particle dissolution. For this purpose, we have utilized the Lattice Boltzmann Method (LBM) as the general framework and integrated Bonded Particle Model (BPM, which is a variation of Discrete Element Model) with immersed moving boundary method.

We have developed a computational platform of particle dissolution in the fluid by utilizing open source LBM C/C++ libraries (Palabos®) and BPM/DEM libraries (LIGGGHTS®). As shown in Figure 1, the fluid phase is evaluated using the Lattice Boltzmann Method. LBM uses the particle distribution function to represent the fluid, from which the velocity and density of the fluid can be calculated [4]. In addition, dissolved drug concentration is computed using a scalar distribution function developed from the lattice Boltzmann method [5]. The fluid-solid interaction is modeled by the immersed moving boundary method [6]. Fluid dynamics exert shear and normal forces on each particle, affecting water uptake kinetics which is modeled by BPM. Dissolution of a particle is based on the advection-diffusion model.

- YL
Yue Li

– Graduate Student, Purdue University, West Lafayette, Indiana - YL
Yue Li

– Graduate Student, Purdue University, West Lafayette, Indiana - TL
Tonglei Li

– Purdue University, West Lafayette, Indiana - YL
Yue Li

– Graduate Student, Purdue University, West Lafayette, Indiana

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