How to make granules
Wet granulation endpoint Determination:
The formulator can define endpoint as a target particle size mean or distribution, or in terms of granulate viscosity or density. It has been shown [26] that once you have reached the desired endpoint, the granule properties and the subsequent tablet properties are very similar regardless of the granulation processing factors, such as impeller or chopper speed or binder addition rate. This can be called “the principle of equifinality”.
The ultimate goal of any measurement in a granulation process is to estimate viscosity and density of the granules, and, perhaps, to obtain an indication of the particle size mean and distribution. One of the ways to obtain this information is by measuring load on the main impeller.
Factors in Wet Granulation include:
- Agglomeration
- Shearing and compressing action of the impeller
- Mixing, granulation and wet massing
- Possibility of overgranulation due to excessive wetting
- Possibility of producing low porosity granules
- Liquid bridges
- Coalescence
- Breakage of the bonds
Due to rapid densification and agglomeration that are caused by the shearing and compressing action of the impeller in a high-shear single pot system, mixing, granulation and wet massing can be done relatively quickly and efficiently. The dangers lie in a possibility of overgranulation due to excessive wetting and producing low porosity granules thus affecting the mechanical properties of the tablets.
As the liquid bridges between the particles are formed, granules are subjected to coalescence alongside with some breakage of the bonds.
Additional Factors in Wet Granulation:
- Specific surface area
- Moisture content
- Liquid saturation
- Intragranular porosity
- Heating
- Evaporation
- Mean granule size
- Apparent viscosity
It stands to reason that mean granule size is strongly dependent on the specific surface area of the excipients, as well as the moisture content and liquid saturation of the agglomerate.
During the wet massing stage, granules may increase in size to a certain degree while the intragranular porosity goes down. However, some heating and evaporation may also take place leading to a subsequent decrease in the mean granule size, especially in small-scale mixers.
Load on the main impeller is indicative of granule apparent viscosity and wet mass consistency.
The following forces act on the particles:
- acceleration (direct impact of the impeller),
- centrifugal,
- centripetal, and
- friction
Why to Monitor Granulator- Mixer?
· Binder addition rate controls granule density
· Impeller speed control granule size and granulation rate
· End point controls the mix consistency and reproducibility
Other factors that affect the granule quality include spray position and spray nozzle type, and, of course, the product composition.
Such variables as mixing time and bowl or product temperature are not independent factors in the process but rather are responses of the primary factors listed above.
For further reading please refer to following book,
Encyclopedia of Pharmaceutical Technology
Third Edition
Publication details, including instructions for authors and subscription information:
Wet Granulation: End-Point Determination and Scale-Up
By Dr. Michael Levin a a Metropolitan Computing Corporation, East Hanover, New Jersey, U.S.A.