Maxim Puchkov
Division of Pharmaceutical Technology, University of Basel
Abstract
Cellular automaton (CA) as a concept of a discrete system was first proposed by von Newmann in late 1940s. The systematic studies, including usage in physical modeling, were investigated by Wolfram in 1980s and resulted in extensive overview and classification on the available types of the cellular automata described in NKS book (Wolfram, New Kind of Science, 2002). Cellular automata is a promising model for heterogeneous particulate system, e.g., a pharmaceutical tablet, consisting of compacted granules or powder mixtures. As a discrete element CA are suitable for modelling of a wide range of physical processes which take place during production of a medicinal product, such as tablets. CA-based models can successfully describe compaction, granulation, dissolution, disintegration and offer realistic simulation platform for such complex processes.
A known drawback of conventional discrete models, e.g., DEM, is memory demand and computational expenses. Such technical limitations significantly influence a number of elements in a simulation. Large systems (N>1Mio) require expensive hardware. Cellular automata offer a convenient and less hardware-demanding opportunity to deal with large and heterogeneous element sets.
The simulation algorithms, based on the cellular automata defined in three-dimensional space, allow simulation of drug-release profiles from a compact taking into account spatial organization of the individual particles. With CA-models it is possible to investigate the effects of granulation, inner and outer phase composition, density of granulates, and resulting compacts; it is possible to see how these effects affect the release pattern of a drug of interest and tablet disintegration. In certain cases the measurement of a key property of a pharmaceutical compact is impossible, such as in-situ measurement of tablet density during dissolution experiment for floating formulations. It is possible to demonstrate how such properties can be calculated for such tablets and analyzed.