Troubleshooting - Granulation Problems and Solutions

Problem:	Solution:
Lumps or oversized Particles Excess product moisture Excess partial product moisture Too sticky polymer Too high local binder concentration	Lumps or oversized Particles Lower the spraying rate Increase inlet air and product temperatures Increase atomizing and microclimate pressure Increase process air flow Check function of the spraying nozzle O-rings Liquid tip, spray air tip
Fines Insufficient product moisture Insufficient local product moisture Instable granules Mechanical Impact Too low local binder concentration	Fines Decrease product temperature Decrease inlet air volume Shorter drying time Lower atomizing and microclimate pressure More appropriate binder Increased binder amounts Higher binder concentration in solution Reduce possible spray drying effect
Width particle size distribution Excess product moisture Excess local product moisture Instable granules Mechanical impact Inhomogeneous granulation (Product falls after the granulation from the dome or filter)	Wide particle size distribution Lower or increase spraying rate Adjust inlet air and product temperatures Adjust product temperatures Adjust atomizing and microclimate pressure Check function of the spraying nozzle Decrease the friability of the granules

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Powder layer at the dome and filters Recondensation Electrostatics and bad flowability Particle size of the starting material Too fine granules	Powder layer at the dome and filters Pre-heating of the fluid bed Adding more water to the spraying liquid Lower inlet air temperature Reduce-spraying rate at beginning Adding of Aerosil to powder mixture before charging Increase microclimate (effect of spray drying) Increase granulation effect Increase inlet air amount in final phase of discharge step
Low yield with clean dome and filters Broken sealing at the filters Damages at the filter socks Starting material is passing the filters	Low yield with clean dome and filters Replace Sealing Replace filter socks, do not repair Use filter socks with Teflon membrane (pore size ~ 1 µm)
Low density of the product Pre-Milling of the starting material Pre-movement of the starting material in the fluid bed Very high product moisture content Prewetting of powder before start of binder application Transfer to RMG	Low spraying rate Reduce the binder concentration Increase the hose size Pre-pressure on binder vessel Heat up the spraying liquid

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No sufficient air supplies Shorten cleaning cycle Increase cleaning pressure Granulate faster Decrease the air amount
Segregation of the product Charge with low inlet air Change excipients (particle size) Start charging good flowable powders Pre-granulate small particles
Inhomogeneity of low-quantity ingredients	Add the ingredient to the granulation liquid
Lumps or oversized Particles in the RMG Excess Product moisture Excess partial product moisture Too excessive granulation	Lumps or oversized Particles Lower spraying rate Increase spraying rate Use the chopper Decrease the liquid amount Faster agitator speed during liquid adding Slower agitator speed during granulation Shorter granulation time Add the liquid by using an atomizing nozzle

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Fines Insufficient product moisture Instable granules Insufficient granulation	Fines Increase spraying rate Increase the liquid amount Faster agitator speed Increase granulation time Inappropriate binder Insufficient binder amounts
Segregation in the RMG	Adjust the agitator speed Adjust mixing time Add the ingredient after wetting
Blockage of the Wet Mill Wrong set up of the mill Product flow to the mill	Blockage of the Wet Mill Increase speed of knife Use wider mesh size Use sieve with square holes Use round knife Decrease the agitator speed during discharge

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