Chemical Engineering Research & Design, Vol.156, 469-477, 2020
Exploring the wet granulation growth regime map - validating the boundary between nucleation and induction
A methodological approach to define the regime map boundaries does not exist, and while some experimental data has been reported previously the boundaries have not been "validated". The present study explored and quantified the boundary between the nucleation and induction growth regimes for a model high drug load formulation. It was postulated that the induction period could be decreased by increasing the liquid saturation of the system, with the effect of introducing additional binder liquid to the surface of the granules, which facilitates consolidation and growth. An increase in liquid saturation was achieved by increasing the liquid to solid ratio, or by densifying the granules to squeeze intragranular liquid to the surface. The densification was achieved by subjecting the granules to an extended wet massing period and by varying the impeller speed. By characterizing the response in granule porosity as a function of liquid to solid ratio, wet massing time and impeller speed the boundary between the nucleation and induction growth regimes was defined. Granules formed in the induction growth regime were shown to suffer significantly reduced compactibility. Further analysis of liquid saturation and compactibility data allows a critical granule porosity to be established as a basis for developing a control strategy. The attention to granule porosity allows a mechanistic interpretation of the growth behavior, rather than simply relying upon size measurements. The porosity based approach was successfully superimposed onto the existing growth regime map framework, and established that the boundary between regimes is a gradual transition rather than the conventionally visualized abrupt binary state. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
Keywords:Wet granulation;Growth regime map;Nucleation;Induction growth;Liquid saturation;Stokes deformation number;Porosity