(356e) Spherical Agglomeration Process: Mechanistic Understanding and Mathematical Modelling | AIChE

(356e) Spherical Agglomeration Process: Mechanistic Understanding and Mathematical Modelling


Smith, R. M. - Presenter, University of Sheffield
Arjmandi-Tash, O., The University of Sheffield
Tew, J. D., The University of Sheffield
Mohd Yusoff, S. N., The University of Sheffield
Pitt, K., University of Sheffield
Litster, J. D., The University of Sheffield
Spherical agglomeration is a specialised process which has recently been successfully applied in pharmaceutical manufacturing, specifically to address problematic properties of irregular platelet- or needle-like crystals such as poor flowability, compressibility and packability. The process involves the precipitation and agglomeration of crystals to produce compact and dense spherical agglomerates. The precipitation is typically achieved by an anti-solvent crystallisation in which an anti-solvent is added to a solvent-drug solution. The agglomeration is achieved by addition of an immiscible bridging liquid into the solution in which the crystals are suspended.

The focus of the current work is on the agglomeration in suspension rate processes as there is no comprehensive mechanistic understanding of this process. Based on the similarities between wet granulation and spherical agglomeration, the following rate processes may be proposed: wetting/nucleation of primary crystals by the bridging liquid, consolidation/growth of agglomerate nuclei, and attrition/breakage of the agglomerates. The aim of the current study is to identify the influence of key material properties and process parameters on the final properties of agglomerates. This was achieved by a) integration of different targeted, systematic small-scale experiments designed to observe and quantify agglomerate evolution, and b) development of predictive and robust mathematical models to inform future process design tools through a bottom-up approach.

Spherical agglomeration experiments were conducted in a stirred vessel and an oscillatory baffled reactor. A novel microfluidic system and a contracting nozzle device were proposed and devised to respectively investigate wetting/nucleation and attrition/breakage of the agglomerates in isolation. A completely novel mathematical model is developed to investigate the kinetics of wetting and nucleation (via an immersion mechanism) and to identify different regimes of the nucleation process. gPROMS FormulatedProducts® was used to develop a population balance model for the agglomeration in suspension process, including a customised agglomeration kernel. The effect of material properties and process conditions on different rate processes, as well as size distribution of the produced agglomerates, was determined through the experiments and the developed models.