A review of regime maps for granulation

Granulation, a size enlargement technique to form agglomerates of primary particles, has proven to be effective in the production of solid dosage forms. Numerous granulation techniques can be applied, such as roll compaction, drum granulation, high shear granulation, twin-screw granulation or fluid-bed granulation.

If the fundamental knowledge about the granule growth mechanism, its impacts as well as their extent and proportions on the mechanism is known, a correlation of the input variables with the granule attributes paves the way regarding a granulation process design and prediction of a systems growth behaviour if one or more affecting parameters change. The dimensionless correlation of the main controlling parameters of the process physics is able to confine an operation window within which different regime areas are defined and where the influencing parameters have different implications on the final product. A regime map is created. The usage of dimensionless numbers ensures a reduction of both the experimental workload and the number of parameters that have to be considered. Thus, a scale-independent operation window can be defined.

The aim of the review is a critical discussion of proposed regime maps for different granulation processes. Continue on regime maps for granulation

Additional publication of interest:

Exploring the wet granulation growth regime map – validating the boundary between nucleation and induction

Highlights

• Wet granulation induction growth has a severe negative effect of compactibility. 

• A novel method to quantify nucleation and induction growth was developed. 

• The transition from nucleation to induction growth was found to be gradual.

•The growth regime can be controlled by liquid saturation and Stokes deformation number.

•  A granule porosity regime map is proposed to better depict the granulation mechanism.

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. Continue on exploring the wet granulation growth regime map