Binder addition methods and binder distribution in high shear and fluidised bed granulation

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

“…scale-up [41]. DEM-CFD or similar based PSD approaches are first principle based models and can be scale independent if the particles are either not scaled or alternatively their properties are scaled to ensure that bulk behavior remains constant.…”

“…Direct discretization is a straightforward approach to obtain an accurate estimate of the particle size distribution, but a disadvantage associated with this methods is the inaccuracy with tracking the moments [41]. Monte Carlo methods are more stochastic in nature and can be used to obtain the solution of multi-component or poly-disperse population balance equation, provided that the probability of dynamic behavior in the system obeys the balance principle for system details, the time step for each successful event can be calculated accurately and all the events occurring in the system are mutually dependant [29,59].…”

“…However a nonlinear grid can span the same range using fewer bins, thus reducing the computational overhead [17]. Various algorithms have been developed to implement a nonlinear grid for discretization [14,40,41,49]. It is most accurate to employ multidimensional PBMs to represent the various particulate processes [38].…”

“…The extent to which this occurs, known as the friability, is measured by tracking the change in mass of the particles as a result of exposure to stress. Instruments such as the Friabilator [41] and the Friabimat [42] simulate the stresses particles experience during processing and handling. Each of these instruments follows the same basic procedure.…”

“…The RSD may be affected by the sample size, and Lacey's Index (M) is a metric that corrects for these effects [40,41], given in Eq. (4), where the subscript s denotes a completely segregated mixture and the subscript r denotes a perfectly random mixture.…”