Types of granulation processes

One of the first steps in the tablet manufacturing process is blending the active pharmaceutical ingredient (API) and the excipients (these are components other than the active substances) until a homogeneous mixture is achieved. Granulation helps with this, and it is done either in a free fall blender or in a high-shear mixer with strong shear forces if the API is low-dose.

Granulation is commonly used in three cases:

1. When simple blending does not produce suitable physicochemical properties, e.g. when the blend has low density or poor flow properties.
2. If the formulation needs special attributes that cannot be achieved with simple blending e.g. gastroresistance, sustained release and taste-masking
3. To add excipients that cannot be mixed in their dry form.

And there are three types of granulation in the pharmaceutical industry: dry granulation (also known as compaction), wet granulation and melt granulation.

Dry granulation

The simple equipment, minimum floor space and processes required for dry granulation make it an efficient inexpensive manufacturing method.

There are some challenges to overcome though, such as ensuring an even particle size distribution and flowability, and avoiding cross-contamination with dust particles released during the process.

Wet granulation

Wet granulation is a widely used tablet manufacturing process in the pharmaceutical industry. Water or an organic solvent is either sprayed or poured into a blend to have its fine particles agglomerated into granules of a desired size with required flow properties.

Wet granulation is often a complex process and involves a variety of equipment and steps such mixing, moistening, screening, drying and sizing.

In essence, the main reason to choose wet granulation is to prepare any combination of drug substance and/or excipients for compression, encapsulation or filling processes, e.g. into sachets.

The two main wet granulation stages are moistening and drying. Both can be carried out in a Fluidized Bed Granulator, or separately – moistening in a High Shear Mixer Granulator and then drying in a Fluid Bed Dryer or Tray Dryer.

Melt granulation:

Melt granulation is a manufacturing method used to enhance the flow properties of the composition and increase the uniformity of the drug.

Melt granulation is usually used when processes like wet and dry granulation do not render the desired results. Its advantages include a continuous and solvent-free process and the omission of a drying step.

In melt granulation, the bioavailability of the drug is modified by adding excipients such as surfactants or crystallization inhibitors; by changing its polymorphic characteristics; or by embedding the drug into a solid dispersion.

The API and excipients are combined to form a dry powder and melted together in a melt extruder. The drug and excipients must be resistant to temperatures over 100°C depending on the formulation and the polymers used for melting.

Other liquids can be added if necessary to predefined areas over the course of the process, which includes different stages (or zones) according to temperature, mechanical stress levels, densification, and backwards movement applied to the melt.

The granulation process is completed as soon as the agglomerated powder particles are cooled, extruded through a dye, cut and solidified.