Application of the flux number approach for the simulation of granulation processes by use of flowsheeting tools

Process Simulation and Data Modeling in Solid Oral Drug Development and Manufacture

“…Thermodynamic models for the prediction of solubility are widely used in the pharmaceutical industry for designing unit operations such as crystallization [72][73][74][75][76][77]. This is because these models are accurate enough to save development time by guiding researchers in the right direction towards desired solubility profiles.…”

“…Mixing is brought about by the particle velocity gradient within the mixer when two or more distinct bulk material particles come into intimate contact. Variability in the mixture is induced by segregation which occurs mainly when particles of different densities tend to settle in different layers [76]. The population balance equation for the mixing process can be written as shown in Eq.…”

“…Han et al [76] performed 2D DEM simulations on a pneumatic conveyor, simulating fragmentation based on impact velocity. Upon impact, if the velocity satisfies criteria, mechanistic correlations for fragment particle size were evaluated.…”

“…The Stochastic Flexibility Index (SF) was introduced by Pistikopoulos and Mazzuchi [76] and Straub and Grossmann [77] in the 1990s. This metric describes the probability that a particular design will achieve feasible operation given uncertainties that are described by a probability distribution.…”

“…For this reason initial solution strategies focused on problems defined by linear constraints [79]. Pistikopoulos and Mazzuchi [76] suggest an approach based on an assumed normal distribution for the joint uncertainty distribution j(θ). By expressing the feasibility function in terms of the Lagrangian, the stochastic flexibility can be determined for a specific set of inequalities k via a one dimensional integral.…”