Complete two dimensional population balance modelling of wet granulation in twin screw

Int J Pharm. 2020 Dec 15:591:120018. doi: 10.1016/j.ijpharm.2020.120018. Epub 2020 Oct 26.

Abstract

In this study, a complete two dimensional (internal coordinates) population balance model (2D-PBM) is developed, calibrated and validated as a predictive tool for predicting the particle size and the liquid content distribution of the granules produced from twin screw granulation (TSG). The model is calibrated and validated using experimental distributions for the two internal coordinates that are captured using image processing. Granulation runs are conducted at multiple liquid to solid (L/S) ratios and liquid binder viscosities, and then used to calibrate and validate the 2D-PBM. The mathematical model accounts for aggregation and breakage of the particles occurring in three zones of the TSG with inhomogeneous screw configurations (2 conveying zones and 1 kneading zone). A Madec aggregation kernel, and a linear breakage selection function are used in the 2D-PBM and finite volume numerical approximation is used for solving the model. The calibrated model shows that the aggregation rate in the conveying elements is higher than in the kneading elements while the breakage rate in the kneading elements is much higher than in the conveying elements. Also, the increase in L/S ratio and liquid viscosity leads to higher aggregation rates and lower breakage rates.

Keywords: 2D-distributions; Finite volume numerical method; Madec kernel; Population balance modelling; Twin-screw granulation.

MeSH terms

  • Bone Screws
  • Drug Compounding
  • Excipients*
  • Models, Theoretical*
  • Particle Size
  • Technology, Pharmaceutical
  • Viscosity

Substances

  • Excipients