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© BASF SE 2013

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: E. Bennie, Active Division, I.M.A. S.p.A., Bologna, Italy

Film-coating Pellets, micro tablets Sugar-coating


(solid wall) film-coating (solid wall)

Film-coating processes can be conducted in various kinds of equipment - there is drum


coating equipment (solid and perforated wall) as well as fluid bed technology.
Th. Cech ǀ E-ENE/PT ǀ Slide: 2 / 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: http://en.wikipedia.org/wiki/Tablet_press

Wrong settings for


the compression
lead to single
tablets which are
out of specification.

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

Weigh in Sieving Blending Compression Film-coating

Weigh in Sieving Granulation Sieving Blending Compression Film-coating

Weigh in Sieving Blending Compression Sieving Blending Compression Film-coating

Weigh in Sieving Granulation Coating Blending Compression Film-coating

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

• Plasticiser • Stirring devices


• Colourant • Spraying system
• pH-value • Temperature

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® SR 30 D 0.04 0.06 45 0.01 45 0.01 47 0.07 54

Kollicoat® MAE 30 DP
0.00 0.02 34 0.06 43 7.50 47 22.54 68
Eudragit® L 30 D-55

Eudragit® NE 30 D 22.96 --- --- --- ---

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

Coagulation of Kollicoat® MAE 30 DP Coagulation can also be achieved by


by adding high concentrated mixing Kollicoat® MAE 30 DP with
propylene glycol Kollicoat® SR 30 D

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

Coagulation of Kollicoat® MAE 30 DP


by adding the colouring agent Sunset
Yellow directly.
Th. Cech ǀ E-ENE/PT ǀ Slide: 10 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Handling of dispersions
Physical / chemical coagulation

Source: Th. Agnese, C. Broicher, Th. Cech, European Application Lab (Pharma Solutions & Human Nutrition), BASF SE, Ludwigshafen, Germany

FD & C Blue No. 1


Carmine (52%)

Sunset yellow

Iron oxide red


Basovit® red

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

• The dispersion might interact with


excipients (e.g. colorant, other
polymers), depending on zeta
potential or pH value these might
result in coagulation

Cures

• Choose the components of your


formulation properly
• Avoid mechanical stress (e.g. pump,
tubing, nozzle)
• Avoid temperature (e.g. stirrer)
• Avoid residuals in the tubing – use
new tubes or ones properly cleaned

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

Nozzle and peristaltic pump


Causes

• Aqueous dispersions of water


insoluble polymers result in low
viscosity
• Too low flow rate (inner diameter of
the tubes to wide) as well as the a
pause in spraying (change of batch)
result in sedimentation

Cures

• Use tubes with an inner diameter


adapted to the spray rate
• Always clean the lines with water
before stopping the spray rate

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

• Al-lakes and dies offer an advantage


regarding sedimentation (small
particles), yet interactions are
possible
• Talk, kaolin, MgS are difficult;
advantages for GMS, but
inconvenient to prepare

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

• Aqueous dispersions of water


insoluble polymers result in low
viscosity
• High AA-pressure in combination
with high inlet air temperatures
results in spray drying

Cures

• Use proper settings such as low inlet


air temperatures (e.g. 55°C) and low
AA-pressures (e.g. 1.2 bar)

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

Coated tablets, sticking together


Causes

• Depending on polymer and amount


of plasticiser tackiness of the film
might occur

Cures

• A proper amount of talc has to be


part of the coat formulation
• Instead of water use a suspension
(e.g. talc or MgS) for finally cleaning
the tubes

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

Kollicoat® MAE 30 DP Kollicoat® Smartseal 30 D


Kollicoat® SR 30 D
formulated dispersion formulated dispersion
solid matter content 20% solid matter content 20%

MFFT relevant component MFFT relevant component


polymer water plasticiser polymer w plasticiser

coating process coating process

Tg relevant component Tg relevant component


polymer plasticiser polymer plasticiser

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

Solid wall coater


Causes

• Functional coatings are either


insoluble or dissolve only in specific
pH values

Cures

• Use proper detergents


• Adjust the pH value according to the
dissolution properties of the
dispersion

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

Discoloured OptiCoat nozzle


Causes

• Discoloration / oxidation of the


nozzle
• Introducing acidic cleaning agents
(e.g. diluted HCl) via the spraying
nozzle may lead to oxidation of he
nozzle body

Cures

• Do not apply acidic cleaning agents


via the spraying nozzle
• Disassemble the nozzle before
cleaning
• Use proper cleaning agents such as
P3 cosa CIP 72 (ECOLAB)

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

The movement of the cores in the drum is influenced by following parameters:

 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

 Formulation of the film-coating dispersion

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

Source: Mixing efficiency in side-vented coating equipment


G. W. Smith, Graeme S. Macleod, John Th. Fell; AAPS PharmSciTech 2003; 4 (3) Article 37

The AccelaCota 24” is


typically used with 10 rpm.
This means: it takes 4
minutes to achieve a
homogeneous mixture.

The mixing characteristics


of the classical rabbit ear
baffles is poor.

Th. Cech ǀ E-ENE/PT ǀ Slide: 21 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Tubular baffle

Source: Mixing efficiency in side-vented coating equipment


G. W. Smith, Graeme S. Macleod, John Th. Fell; AAPS PharmSciTech 2003; 4 (3) Article 37

The ‘Tubular Baffle’ is much


more efficient.

Th. Cech ǀ E-ENE/PT ǀ Slide: 22 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Baffles and their mixing behaviour
Mixing efficiency

Source: G. W. Smith, BOSCH Manesty, Knowsley, UK


Pictures: W.-D. Fischer, Glatt AG, Pratteln, Switzerland; BOSCH Manesty, Knowsley, UK

Type of baffle Mixing effect Mixing Usage

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

Source: S. Gerstner, Düsen-Schlick GmbH, Untersiemau/Coburg, Germany

Classical two substance horn


nozzle, like distributed from
different manufacturers
(e.g. Schlick, Manesty, Walter,
…)

New developed ABC nozzle,


distributed from Schlick and
with a similar configuration
from Glatt.
This cap is very successful in
the market and substitutes
the old configuration in many
applications.

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

Source: S. Gerstner, Düsen-Schlick GmbH, Untersiemau/Coburg, Germany

Schlick horn nozzle - Schlick ABC nozzle -


Classical set-up (ABC = anti bearding cap)

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

Source: W.-D. Fischer, Glatt AG, Pratteln, Switzerland

Schlick horn nozzle -


Visualisation of airborne droplets

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

Source: W.-D. Fischer, Glatt AG, Pratteln, Switzerland

Schlick ABC nozzle -


Visualisation of airborne droplets

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)

Source: S. Gerstner, Düsen-Schlick GmbH, Untersiemau/Coburg, Germany

without flat air

too much moisture


in the central zone

extremely high flat air pressure

too much moisture


in the outer rim

optimal spray pattern

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

Source: W.-D. Fischer, Glatt AG, Pratteln, Switzerland

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

Source: W.-D. Fischer, Glatt AG, Pratteln, Switzerland

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

Perforated drum coater Also very important for a


successful coating
process is the gun to
wall distance.
A wrong positioning
leads to a coated wall,
the coating result is
badly influenced.

Th. Cech ǀ E-ENE/PT ǀ Slide: 31 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Positioning of the nozzles

Distance Angle Position


nozzle core bed nozzle core bed in the drum

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

Source: S. Gerstner, Düsen-Schlick GmbH, Untersiemau/Coburg, Germany

Bore diameter
[mm]
Spray rate
[g/min]
Viscosity < 100 mPas Viscosity > 100 mPas

0.8 – 1.0 1.0 – 1.2


30 – 60
AA start at 0.7 bar
1.0 – 1.2 1.2 – 1.5
60 – 120
AA start at 1.0 bar
1.2 – 1.5 1.5 – 1.8
120 – 150
AA start at 1.5 bar
1.5 – 1.8 1.8 – 2.2
150 - 180
AA start at 2.0 bar
Th. Cech ǀ E-ENE/PT ǀ Slide: 33 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Nozzle technology
Pumping

Video: S. Gerstner, Düsen-Schlick GmbH, Untersiemau/Coburg, Germany


Pictures: www.wikipedia.org

Rotary type Schlick ABC nozzle


prototype

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

Source: W.-D. Fischer, Glatt AG, Pratteln, Switzerland

Also important for the coating


quality is the positioning of the
exhaust air shoe and the batch
quantity respectively.

Wrong settings lead to a worse air


flow resulting to over wetting.

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

Defilement of the drum


perforation (caking) may
lead to changes in the air
flow. The increasing
aerodynamic resistance
leads to an increasing
pressure in the drum and
potentially to turbulences
(spray drying effects).

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

• Process time too short


• Solid matter content too high
• Poor mixing behaviour (drum)
• Dispersion not homogeneous

Cures

• Increase process time


(decrease spray rate)
• Improve mixing behaviour
(increase drum speed)
• Stir dispersion during coating

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

• Colouring agent is light-sensitive


• Chemical interaction with core
components

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

• Slow drying process


• Spray rate too high
• Air quantity too low
• Temperature too low
• Positive air pressure in the drum
• Guns too close together

Cures

• Increasing inlet air quantity and


temperature
• Reducing spray rate
• Increasing exhaust air quantity
• Increasing drum speed
• Adapt gun to gun distance and air
pressure

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

• Moisture content too high


• Product temperature too high
(depending on polymer (Tg))
• Initial twinning
(depending on core formulation)
• Shape of the cores

Cures

• Reduce spray rate


• Increase bed temperature
• Increase inlet air temperature
• Increase inlet air quantity
• Interval spraying

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

• Swelling of the core


• Moisture content too high
• Insufficient plasticizer content
(depending on type of polymer)

Cures

• Reduce spray rate


• Increase bed temperature, inlet air
temperature or inlet air quantity
• Adapt coating formulation
• Usage of other plasticizers

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

• Swelling of the core


• Tablets shows elastic deformation,
which is time dependent
• Sometimes elastic deformation is
temperature initiated

Cures

• Do not coat tablets directly after


compression (continuous
manufacturing is crucial)
• Store tablets > 1 day before coating
• Alteration of process temperature
might be considered

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

• Product temperature too high


(excipients with low melting point)
• Moisture content too high
(easy soluble excipients)

Cures

• Reduce product temperature


• Reduce moisture content during
coating process

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

• Dust formation due to spray drying


 process temperature too high
 wrong position of the nozzle
 wrong nozzle type (bore)
• Dust formation, due to high friability
• Air stream not optimal
• Low adhesion of the film

Cures

• Adjusting process parameters


 quantity
 temperature
• New positioning of the nozzle
• Solid content too high
• Using other type of nozzle (bore)

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

• Moisture content during the film-


coating process is too high,
therefore disintegrant (Kollidon® CL)
showed swelling

Cures

• Spray intervals in the beginning of


the process
• Increasing core bed temperature
Usage of:
Kollidon® CL-F
Kollidon® CL-SF

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

• Decreasing solid matter content


• Reformulation of coating dispersion
• Increasing atomisation air pressure
• Using other nozzle design (bore)
• Adapt engraving design
(angle, depth)

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

• Pigments are agglomerated


• Coagulation
• Dispersion not homogeneous

Cures

• Using high shear mixer for


preparation
• Prevent shear stress

Th. Cech ǀ E-ENE/PT ǀ Slide: 50 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Magnetic pigments

Source: F. L. Ikuno; BASF SE; Brazil

Stirring device (beaker)


Causes

• Pigments (e.g. iron oxide black) is


magnetic

Cures

• Use other types of stirrer


(e.g. over head stirrers)
• Use pigments which are not
magnetic

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

• Hardness and friability not sufficient


• Drum speed too high
• Process time too long
• Sharp tablet edges

Cures

• Reducing drum speed


• Increasing hardness of the cores
• Reducing mechanical stress
(shorter process time by increasing
spray rate)
• Usage of other tablet shapes

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

• Process time too long


• Drum speed too high
• Hardness and friability not sufficient
• Shape of tablets
• Overwetting

Cures

• Reducing drum speed


• Increasing hardness of the cores
• Reducing mechanical stress
(shorter process time by increasing
spray rate)
• Adapt spray rate (overwetting)

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

• Glass transition temperature (Tg) of


the polymer is reached, provoking
stickiness

Cures

• Usage of alternative plasticizers


• Usage of lower amount of
plasticizers
• Reduce inlet air temperature
(this effect is NO overwetting!)
• Increase air volume (drum coating)

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

Talk (E 553 b) Kaolin (E 559)

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

Specific density 2.58 – 2.83 Specific density 2.61 – 2.68


Mean particle size Ø 10 - 20 µm Mean particle size Ø 0.5 – 1.0 µm
Hardness (Mohs) 1 – 1.5 Hardness (Mohs) 2.0 – 2.5
Th. Cech ǀ E-ENE/PT ǀ Slide: 55 / 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

Titanium dioxide (E 171) Caused by the high hardness of


titanium dioxide, the equipment can
be ‘cleaned’ with coating. Hereby,
particles are being attached to the
surface.

Specific density 3.8 – 4.1


Mean particle size Ø 1.05 µm
Hardness (Mohs) 5–6
Th. Cech ǀ E-ENE/PT ǀ Slide: 56 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Scuffing

Source: www.wikipedia.org

Mohs Vickers absolute


hardness
Mineral Structure
hardness hardness
Hardness of some items

1 Talc Mg3Si4O10(OH)2 2.4 0.03 2.5 Fingernail


2 Gypsum CaSO4·2H2O 36.0 1.25 2.5–3 Gold, Silver
3 Calcite CaCO3 109.0 4.5 3 Copper penny
4 Fluorite CaF2 189.0 5.0 4-4.5 Platinum
5 Apatite Ca5(PO4)3(OH-,Cl-,F-) 536.0 6.5 4-5 Iron
6 Orthoclase KAlSi3O8 795.0 37 5.5 Knife blade
7 Quartz SiO2 1,120.0 120 6-7 Glass
8 Topaz Al2SiO4(OH-,F-)2 1,427.0 175 6.5 Iron pyrite
9 Corundum Al2O3 2,060.0 1,000 7+ Hardened steel file
10 Diamond C 10,060.0 140,000 2.5 Fingernail
Th. Cech ǀ E-ENE/PT ǀ Slide: 57 / 59 Pharma Solutions Sales Europe Nutrition & Health Division
Typical obstacles
Summary

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)

Phone: + 49 (0) 621 / 60 – 99 290


Mobile: + 49 (0) 173 / 347 99 58
Fax: + 49 (0) 621 / 60 – 66 99 290

Mail: thorsten.cech@basf.com

Internet: www.pharma.basf.com
www.newtrition.basf.com

Th. Cech ǀ E-ENE/PT ǀ Slide: 59 / 59 Pharma Solutions Sales Europe Nutrition & Health Division

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