Mechanistic Modelling of Fluid Bed Granulation, Part I: Agglomeration in Pilot Scale Process

Publication date: Available online 9 November 2019Source: International Journal of PharmaceuticsAuthor(s): Maryam Askarishahi, Martin Maus, Daniela Schröder, David Slade, Michael Martinetz, Dalibor JajcevicAbstractThe present study aims to develop a mechanistic model to predict the performance of a fluid bed granulation process. Therefore, the behavior of the bed was investigated experimentally for various operating conditions. It was observed that the granule Loss on Drying (LoD) and granule size are strongly interrelated. In detail, the maximum final granule size was observed at an intermediate final LoD. Consequently, there is an optimum spray rate and inlet temperature with respect to the granule size. Besides, it was demonstrated that the experiments delivering lower LoD result in a more elongated final granule. Aimed at enabling the prediction of the bed performance numerically, a single-compartment, population-balance-based model was developed and validated against experimental data. The model parameters associated with the growth rate of granule were estimated and mechanistically correlated to the relevant operating conditions. Detailed analysis of the experimental results suggested that these model parameters may be partially connected to the granule LoD. Subsequently, in order to examine the accuracy of the developed model, a simulation was performed for a new set of operating conditions not previously accounted for in the correlations. The comparison of the simula...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research