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07 - Film Coating Trouble Shooting
07 - Film Coating Trouble Shooting
Thorsten Cech
Manager European Application Lab
Pharma Solutions & Human Nutrition
Europe, Africa, West Asia
Trouble shooting -
obstacles during film-coating
Introduction
Variety of film-coating technology
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Picture: http://en.wikipedia.org/wiki/Tablet_press
Th. Cech ǀ E-ENE/PT ǀ Slide: 3 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Introduction
Why is a perfect film-coating process that important?
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Picture: F. A. Rowley; Presentation: Engineering for Success: The Aqueous film-coating Process; Los Angeles, 2005
Film-coated tablets, sticking together due Film-coated tablets, sticking together due
to poor coating formulation to over-wetted process
Wrong settings for the compression lead to single tablets which are out of specification.
Wrong settings in the coating process lead to the loss of the whole batch!
Th. Cech ǀ E-ENE/PT ǀ Slide: 4 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Introduction
Importance of the process
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Th. Cech ǀ E-ENE/PT ǀ Slide: 5 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Processing of dispersions
Typical obstacles
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
• Temperature • Stirrer
• Temperature • Plasticiser
alterations incorporation
• Exposure to • Duration
sunlight
Storage,
Preparation
shipment
Formulation Processing
Th. Cech ǀ E-ENE/PT ǀ Slide: 6 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Physical coagulation (1)
Source: Th. Agnese, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Coagulation [%]
Found after stressing the dispersion with a high shear mixer
(UltraTurax 25)
Speed
[rpm] 2,000 11,000 13,000 16,000 19,000
temp. temp. temp. temp.
Time [°C] [°C] [°C] [°C]
[minutes] 15 4 4 4 4
Kollicoat® MAE 30 DP
0.00 0.02 34 0.06 43 7.50 47 22.54 68
Eudragit® L 30 D-55
Th. Cech ǀ E-ENE/PT ǀ Slide: 7 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Physical coagulation (2)
Source: Th. Agnese, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Eudragit® NE 30 D Eudragit® NE 30 D
(without shearing) (15 minutes / 2,000 rpm)
Th. Cech ǀ E-ENE/PT ǀ Slide: 8 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Physical / chemical coagulation
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Th. Cech ǀ E-ENE/PT ǀ Slide: 9 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Physical / chemical coagulation
Source: Th. Agnese, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Kollicoat® MAE
Sicovit® E110
Source: Th. Agnese, C. Broicher, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Sunset yellow
Patent blue
Erythrosine
Tartrazine
Blank
E124
E120
E131
E172
E127
E102
E110
TAC 24 h OK OK 24 h 24 h 24 h OK OK 24 h
TBC OK OK OK OK OK OK OK OK OK
ATBC OK OK OK OK OK OK OK OK OK
TEC OK 48 h OK OK 48 h OK OK 24 h 48 h
DBS OK OK OK OK OK OK OK OK OK
Kollisolv® P124 OK OK OK OK OK OK OK OK OK
PEG 6000 24 h 24 h 24 h 24 h 24 h 24 h 24 h 24 h 24 h
Th. Cech ǀ E-ENE/PT ǀ Slide: 11 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Coagulation
Source: Th. Agnese, C. Broicher, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Coagulated dispersion
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 12 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Sedimentation
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Pictures: B. Helsdon, Bosch (Manesty), Knowsley, U.K.; www.wikipedia.org
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 13 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Sedimentation
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Stokes’ law
Causes
d ⋅ (ρ p − ρ s )⋅ g
• Due to low viscosity of dispersions ,
2 sedimentation tendency is always
p
vs = high
18 ⋅η
• The larger the pigments, the faster
the sedimentation
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 14 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Spray drying
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Glatt nozzle
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 15 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Bulk stability
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 16 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Tg – responsible parameter for tackiness
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
In case of MAE and SR one Tg relevant plasticiser (water) is evaporated during the coating
process. The likelihood for tackiness is higher for Smartseal. Therefore, a ‘top-coat’ is
recommended (MgS).
Th. Cech ǀ E-ENE/PT ǀ Slide: 17 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Cleaning
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 18 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Cleaning
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 19 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Parameters influencing the product movement
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Type of coaters
Size and shape of the drum
Baffle -
numbers of baffles and design
Drum speed
Batch size in ratio to the capacity of the coaters
Shape and size of the cores
Density of the core
Th. Cech ǀ E-ENE/PT ǀ Slide: 20 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Rabbit ear baffles
Th. Cech ǀ E-ENE/PT ǀ Slide: 21 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Tubular baffle
Th. Cech ǀ E-ENE/PT ǀ Slide: 22 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Mixing efficiency
long
processes,
Rabbit ears low gentle
highly friable
tablets
low batch
Ploughshare intermediate moderate
sizes
short
processes,
Tubular very high aggressive
lowly friable
tablets
Th. Cech ǀ E-ENE/PT ǀ Slide: 23 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Comparison of ‘old’ and ‘new’ air caps
Th. Cech ǀ E-ENE/PT ǀ Slide: 24 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Comparison of ‘old’ and ‘new’ air caps
Th. Cech ǀ E-ENE/PT ǀ Slide: 25 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Comparison of ‘old’ and ‘new’ air caps
Th. Cech ǀ E-ENE/PT ǀ Slide: 26 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Comparison of ‘old’ and ‘new’ air caps
Th. Cech ǀ E-ENE/PT ǀ Slide: 27 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Settings for flat jet air (pattern air)
homogenous distribution
of the dispersion
Th. Cech ǀ E-ENE/PT ǀ Slide: 28 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Nozzle positioning
Product pan
Spray
ellipsoid
Spray nozzle
Spray jet of
solution liquid
Product
Th. Cech ǀ E-ENE/PT ǀ Slide: 29 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Nozzle positioning
Product pan
Spray
ellipsoid
Spray nozzle
Spray jet of
solution liquid
Product
Th. Cech ǀ E-ENE/PT ǀ Slide: 30 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Nozzle positioning
Source: F. A. Rowley; Presentation: Engineering for Success: The Aqueous film-coating Process; Los Angeles, 2005
Th. Cech ǀ E-ENE/PT ǀ Slide: 31 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Positioning of the nozzles
1/3
2/3
90°
The distance between nozzle and core bed should be about 20 – 23 cm.
The nozzle should be adjusted in an angle of about 90°.
The positioning of the nozzle should be as high as possible.
It is of great importance, that the cores already reached their maximum speed
Th. Cech ǀ E-ENE/PT ǀ Slide: 32 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Typical settings for S45
Bore diameter
[mm]
Spray rate
[g/min]
Viscosity < 100 mPas Viscosity > 100 mPas
Linear type
Th. Cech ǀ E-ENE/PT ǀ Slide: 34 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Tubing sizes
Source: B. Weiland, Heidolph Elektro GmbH & Co. KG, Kelheim, Germany
Tubing sizes
Inner diameter 0.8 mm 1.7 mm 3.1 mm 4.8 mm 6.3 mm
Outer diameter 4 mm 4.9 mm 6.3 mm 8 mm 9.5 mm
Wall thickness (wt) 1.6 mm 1.6 mm 1.6 mm 1.6 mm 1.6 mm
Max. pressure 0.7 / 1.7 bar 0.7 / 1.7 bar 0.7 / 1.7 bar 0.5 / 1.5 bar 0.5 / 1.5 bar
Flow rates in combination with pump head / pump drive [mL/min]
min. max. min. max. min. max. min. max. min. max.
PD 5106 / 5206 1.6 40 6.8 169 25.7 643 56 1,400 88.7 2,217
PD 5006 3.3 40 14.1 169 53.6 643 116.7 1,400 184.8 2,217
PD 5101 / 5201 0.3 8.0 1.4 34 5.2 129 11.2 280 17.7 443
PD 5001 0.7 8.0 2.8 34 10.7 129 23.3 280 37.0 443
PD 5106 / 5206 2.4 60.2 10.4 260 41.2 1,029 86.3 2,157 146 3,644
PD 5006 5.0 60.2 21.7 260 85.8 1,029 179.8 2,157 304 3,644
PD 5101 / 5201 0.5 12.0 2.1 52 8.2 206 17.3 431 29.2 729
PD 5001 1.0 12.0 4.3 52 17.2 206 36.0 431 60.7 729
Th. Cech ǀ E-ENE/PT ǀ Slide: 35 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Overwetting, caused by wrong batch size
Th. Cech ǀ E-ENE/PT ǀ Slide: 36 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Overwetting, caused by poor coater settings
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Germany
Picture: W.-D. Fischer, Glatt AG, Pratteln, Switzerland
150 Pa
1.5 mbar
1.125 mm Hg
0.0443 inch Hg
0.00148 atm
0.0218 PSI
It is important to run the coating process with depression. This assures that moisture content
of the process air does not increase in the drum.
Th. Cech ǀ E-ENE/PT ǀ Slide: 37 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Overwetting, caused by blockage of the perforation
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Germany
Pictures: W.-D. Fischer, Glatt AG, Pratteln, Switzerland
Th. Cech ǀ E-ENE/PT ǀ Slide: 38 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Colour variations
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 39 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Bleaching
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
• Light protection
(packaging material)
• Using other colouring agents
Th. Cech ǀ E-ENE/PT ǀ Slide: 40 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Sticking
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 41 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Sticking – twinning, picking
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 42 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Cracking
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 43 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Cracking
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 44 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Cratering
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 45 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Peeling
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
• Poor adhesion
(e.g. hydrophobic cores)
Cures
• Increase adhesion
(e.g. add silica dioxide)
• Reformulation
Th. Cech ǀ E-ENE/PT ǀ Slide: 46 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Orange peel, roughness
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 47 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Orange peel, roughness
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 48 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Bridging, logo filling
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Photo: F. A. Rowley; Presentation: Engineering for Success: The Aqueous film-coating Process; Los Angeles, 2005
Tablet examples
Causes
• Viscosity to high
• Poor polymer properties
• Peeling
• Spray drying
• Pigment concentration too high
• Solid content too high
• Big droplets
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 49 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Colour variation (spots)
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 50 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Magnetic pigments
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 51 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Edge chipping, capping
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 52 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Core erosion
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Tablet examples
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 53 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Tg of the polymer
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Pictures: D. van den Heuvel; Synthon BV; Nijmegen; The Netherlands
Wurster coating
Causes
Cures
Th. Cech ǀ E-ENE/PT ǀ Slide: 54 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Scuffing
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Values: A. H. Kibbe; Handbook of Pharmaceutical Excipients
Mg (OH) [Si O
6 4 8
]
20
Al (OH) [Si O
4 8 4 10
]
Mg [Si O
3 4 10
] ⋅ (OH) 2
Al Si O ⋅ (OH)
2 2 5 4
Source: Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany
Values: A. H. Kibbe; Handbook of Pharmaceutical Excipients
Source: www.wikipedia.org
Source: F. Wildschek, Technical Marketing Pharma Solutions Sales Europe Europe, Lampertheim, Germany
Checklist –
Most critical parameters for the coating process
Gun geometry
Atomizing / flat jet air
Pan pressure
Pan speed
Spray rate
Inlet / exhaust air temperature
Total air volume
Adhesion of particles to the spray gun
Th. Cech ǀ E-ENE/PT ǀ Slide: 58 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Contact
Thorsten Cech
Manager European Application Lab
Pharma Solutions & Human Nutrition
BASF SE
E-ENE/PT – Nutrition & Health (Europe, Africa, West Asia)
Mail: thorsten.cech@basf.com
Internet: www.pharma.basf.com
www.newtrition.basf.com
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