Pharmacy Courses

Granulation End Point Determination

Granulation is a core part of pharmaceutical manufacturing. Because various physical and chemical properties of drug product depend on granules character. For example, granules flow properties, tablet hardness, tablet disintegration timr and content uniformity highly depends on granules characteristics.

That's why proper granulation is a fundamental need for drug product. But which parameter indicate the wet granulation end point? when do you need to stop massing or stop with the addition of granulating liquid? what is the correct amount of granulating liquid? This is the topic for discussion here.

End Point in a wet granulation process is characterized by few properties of the wet mass such as granules density, viscosity, strength, binding etc. Which are in turn a function of particle size, shape, density and other physical properties.

There are few indicators to determine the granulation end point in high shear mixer or granulator (HSG). Where include-

  • Manual observation (granules strength, density etc.)
  • Machine reading (current consumption, calculated torque etc.)
  • Mixing time & impeller speed
It is commonly known that the wet mixing step has the greatest impact on determining the endpoint. However, the granulating fluid/binder solution addition phase and binder addition method also play important roles in granule formation. So, when predicting the endpoint of granulation, the binder addition phase must be considered along with the wet mixing phase.  

In FBD (fluid bed processor), granulation end point determined by physical observation of granules. It's depends on spraying time, speed, atomization air pressure and granulating fluid amount.

End-Point Reproducibility 

Though it is difficult to detect the endpoint of granulation with achieving reproducible manner but with proper controlling a range of critical process variables it can be achieved. Process variables include - mixer geometry, blade speed, powder volume, amount and method of addition of granulating liquid.

CPP for Wet Granulation

Critical Process Parameters in HSG/RMG
  • Impeller RPM
  • Chopper RPM
  • Mixing Time

Critical Process Parameters in FBD
  • Inlet Temperature                 
  • Product Temperature            
  • Exhaust Temperature 
  • Air flow
  • LOD %      

Ultimate goal of any measurement in a granulation process is to estimate the density and viscosity of the granules and particle size of distribution.

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