A mechanistic population balance model for granulation processes: Effect of process and formulation parameters

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.…”

“…Many published breakage kernels have been presented in literature, one of which defines the breakage kernel in terms of empirical parameters and shear rate [64]. Mechanistic kernels have also been proposed in literature, where the kernel has 64 Anwesha Chaudhury et al been expressed to be proportional to the ratio of the external stress to the intrinsic strength [73]. Several models have been developed in order to quantify the breakage distribution function [65].…”

“…A more mechanistic approach towards obtaining the breakage kernel has also been proposed by Ramachandran et al [73] where the K break has been represented as a ratio of the external stress to the internal stress. These stresses have been further obtained by applying the physics of the system combined with the information of the various microscopic properties.…”

“…The breakage rate kernel depends on the material properties of the formulation, as well as the process conditions. While these kernels are empirical, a mechanistic breakage kernel for granulation was developed by Ramachandran et al [73] and can be applied to milling processes. Similarly, various breakage distribution functions have been proposed, including the Hill-Ng distribution [25], a bimodal lognormal distribution [78], and a lognormal distribution [3].…”

“…Additional studies using this methodology were performed by Subero et al [66], Thornton et al [67], Mishra and Thornton [68], Moreno et al [69], Golchert et al [70], Antonyuk et al [71], Hassanpour et al [72], and Tong et al [73]. DEM simulations can also be used to collect particle scale information to use in a process-scale breakage model.…”