Computer simulation of tablet dissolution

Tereza HerinkováZdeněk Grof, František Štěpánek

The kinetics of API (active pharmaceutical ingredient) release is determined by the structure of a pharmaceutical tablet and can be characterized and reported in the form of release curve during a single experiment. On the contrary, to determine the structure of the tablet which would match the required release curve, many tablets with different structures have to be produced and tested. The design of tablet formation process is therefore a costly procedure consuming substantial amount of API and requiring a lot of time as well.

We are developing a mathematical model able to determine the dissolution behavior of a given pharmaceutical tablet. The tablet is characterized by its shape, spatial distribution of components and other physical properties determining its interaction with solvent.

In order to capture the change of tablet shape due to tablet swelling and disintegration during the dissolution process, DEM (Discrete Element Method) is used and the virtual tablet is discretized into a network of connected spherical elements, each element described by its position, size and composition. After force interactions and diffusion fluxes between all pairs of elements are determined, the momentum and mass balances formulated for each element govern element’s movement and size evolution. As the result, the model is able to keep track of the tablet size and shape, the concentration profiles inside the tablet and the history of release rate of API from the virtual tablet during its dissolution.

Our model is validated by comparing its predictions with MRI scans observing the dissolution of real pharmaceutical tablets.

Publications:

  1. Grof Z., Štěpánek F., “Quantifying the effect of fillers on the breakage behaviour of needle-shaped particles”, Adv. Powder Technol., in press (2016)
  2. Gajdošová M., Pěček D., Sarvašová N., Grof Z., Štěpánek F., “Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging”, Int. J. Pharm. 500, 136-143 (2016)
  3. Grof Z., Štěpánek F., “Distribution of breakage events in random packings of rodlike particles”, Phys. Rev. E 88, 012205 (2013)

Conference poster presentations:

  1. pdfHerinková T., Grof Z., Štěpánek F. Modelování inženýrských procesů v chemické robotice, CHISA 2015, Seč u Chrudimi, Czech Republic