4.basf - 855 - e 17 (TC) - Ima Spain - Up Scalin

Scaling up
a film-coating process
Thorsten Cech
Manager European Pharma Application Lab,
Pharma Ingredients & Services,
Nutrition & Health Division
G-ENP/ET
The up-scaling problem

Introduction
Source: Brian Helsdon, OYSTAR Manesty, Knowsley, U.K.
Up
Upscaling
scaling
Manesty XL Lab 02
Premier 900
15 kg
Batch size
850 kg
420 m/h
Inlet air quantity
10,000 m/h
60C
Inlet air temperature
60C
Spray guns
42 g/min
Spray rate
???
Pharma Ingredients & Services
T. Cech - G-ENP/ET - page 2

Practical example (Kollicoat IR formulation)
Source: Scale-up of an instant release film coating process with Kollicoat IR
K. Kolter; BASF SE; AAPS Annual Meeting; October 21 24, 2001; Denver; Colorado; U.S.A.
AccelaCota
Driacoater
Batch size
[kg]
15
250
Spray rate
[g/min]
14
42
700
[g/min/kg]
2.8
2.8
2.8
[m/h]
83
223
4,400
16.6
14.9
17.6
[C]
71
73
70
Exhaust air temperature [C]
47
50
47
Rel. spray rate

Inlet air quantity
Rel. inlet air quantity[m/h/kg]

These trials show the

linear approach
.
Both relative spray rate and relative inlet air quantity are kept constant in all
scales.

Typical parameters for Glatt coaters in different scale
1,400
7,000
1,200
6,000
1,000
5,000
800
4,000
600
3,000
400
2,000
200
1,000
Process air quantity [m/h]
Spray rate [g/min]
Source: Thorsten Cech, European Pharma Application Lab, BASF SE, Ludwigshafen, Germany
Data:
Wolfgang Dejan, Glatt AG, Pratteln, Switzerland
The chart displays the

recommended spray
rate
and
the
commonly
used
process air quantities
in different scales for
horizontal side vented
pan coaters of Glatt.
0
0
100
200
300
400
500
600
700
800
Batch size [kg]

Recommended maximum spray rate
Commonly used process air quantity
This chart shows the non-linear reality.

There is no linear slope in spray rate and process air quantity during the up
scaling step.

Typical parameters for Glatt coaters in different scale
6.0
90
5.0
75
4.0
60
3.0
45
2.0
30
1.0
15
0.0
Process air quantity [m/h]
Spray rate [g/min]
Data:
Wolfgang Dejan, Glatt AG, Pratteln, Switzerland
The chart displays the

relative spray rate and
the relative process air
quantities in different
scales for horizontal
side
vented
pan
coaters of Glatt.
0
1
10
100
1000
Batch size [kg]

Recommended maximum spray rate
Commonly used process air quantity
The available relative process air volumes are decreasing during up scaling.
For this, the relative spray rate cannot be a constant, for economical
processes. However, low relative spray rates can be used in small scale.

Summary
In typical side vented pan coaters, the available relative process air
volume (m/h/kgcores) is higher in small scale than in large scale.
As a result of this, the relative spray rate (g/min/kgcores) can easily be
used for down scaling of film coating processes. The likelihood for
overwetting is low but the risk for spray drying is increased.
A relative spray rate found and optimised for small scale coaters can
hardly be used in production scale.
The coating process in different scales

General Scale Up Consideration
Source: Elisa Bennie, Active Division, I.M.A. S.p.A., Bologna, Italy
Armin Bohle, Lbb Bohle Maschinen & Verfahren GmbH, Ennigerloh, Germany
Lab scale
Batch size:
Nozzles:
0.5 8.5 kg
1
Pilot scale
Batch size:
Nozzles:
25 50 kg
2 5
Production scale
Batch size:
Nozzles:
>150 kg
3 - 15
The coating process in different scales

Summary
The Process-Parameter-Chart can be considered as perfect tool to

compare different types of coaters, varying formulations or different types
of process set-ups.
The process time prolongs during scale up procedures.
Main reason for the prolonged process time is the difference in batch to
nozzle ratio during up scaling. The amount of cores per nozzle is
increasing.
The film coating process

Parameters influencing the film coating process
Quelle: O
HARA
Drawing: Dori Schmetterling, O
Hara, Richmond Hill, Canada
Exhaust air
Inlet air
Temperature
Quantity
Humidity
Temperature
Quantity
Humidity
Drum
Cores
Size
Shape
Hardness
Friability
Roughness
Temperature
Nozzle
Formulation
Design (e.g. ABC)

Number
Angle
Distance
Spray rate
AA-pressure
PA-prressure
Type (e.g. solid)

Size
Speed
Filling degree
Surface
Baffles
Temperature
Polymer(s)
Additives
Solvent
Viscosity
Solid matter cont.
Stickiness
Film properties

Visualization of the film coating process
Drawing: Alexander Rongen, Glatt GmbH, Binzen, Germany
Begin of the
coating process
Core particle
Film building process
Droplets of the film coating dispersion
Finally formed filmed


Thermodynamic consideration of the core temperature
Product temperature
Source: Investigating the up scaling properties of a sustained-release coating using side vented pan coating technology
Agnese, Cech, Cembali, Funaro, Mondelli, Wildschek; 7th PBP World Meeting; March 8 - 11, 2010; Valletta, Malta
Time of process cycle
Steady state core bed temperature

Spray pattern, liquid carrier gets
applied
Core is completely dried, when
immersing into the core bed again
Core took up energy and reached
steady state temperature again

Thermodynamic consideration of the process air temperature
Process air temperature and humidity
Temperature
Relative humidity
Time of process air in the process
Drop in inlet air temperature due to

convection
Passing spray pattern and transferring energy for evaporating the
liquid carrier
Transfer energy to heat up core
bed to steady state temperature
Energies inlet air temperature

Equipment schema
Drawing: Elisa Benni, I.M.A. S.p.A., Active Division, Bologna, Italy
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Dispersion tank
Peristaltic pump
Guns adjustment system
Coater
Spray guns
Inlet air unit
Control panel
Dust collector
Outlet air fan
Inlet air unit
Inlet air Unit:
Filter
Conditioning
(humidifying and de-humidifying)
Heating

Energies needed for the process air
=10C
Required energy supply

in
ambient
heat
de-humidification
160
Calculation background
140
Efficiency heater:
100%
Losses of heat:
0%
50C
120
Energy supply [kW]
Dew point:
10C/100% r. h. = 7.6 g/kg
60C
100
70C
80
60
40
20
0
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
Inlet air quantity [m/h]

Energies needed for the process air
& = 3,869 kgh

m
& = 3,793 kgh

m
& = 3,793 kgh

m
T = 35C
3
V& = 3,383 mh
T = 60C
3
V& = 3,600 mh
T = 10C
3
V& = 3,060 mh
Y = 12.7 kgg
Y = 7.6 kgg
Y = 7.6 kgg
V&in
V&out
AA: 2.2bar, 80L/min

PA: 2.2bar, 100L/min
Spray rate:
Solid content:
Water:
400 g/min
20%
19.2 kg/h
Energies inlet air quantity

The drying of the dispersion on the core surface
Source: Comparison of Film Coating Process using fully perforated and partly perforated Coating Pans
Lirong Liu (Pfizer), Timothy J. Smith, Gary L. Sackett (Vector), Ethel Poir (Micro Photonics), Paul Sheskey (Dow)
Conclusions
In this study, the partially
perforated pan required a
lower inlet temperature (at the
same air volume and spray
rate) to maintain the same
exhaust temperature when
compared to fully perforated
pan.

Source: Scaling up in Film Coating Processes
Thorsten Cech, Florian Wildschek; BASF SE; ExcipientFest Europe, June 17./18., 2008, Cork, Ireland
Drying process
c (T T )
h
Q& = A v ln1 + p,D 2 1
hv
c p,D
The
heat transfer coefficient ()
depends on the air velocity.
Q& A (Tap Tac )
1
c 0
v v lam
2
1 +
Pr 3 1
v
= f (v air )

Source: Technische Strmungslehre
Willi Bohl; 12. Auflage; 2001; VOGEL; Germany
Bernoulli's law derivation diagram
g hinlet
pair ,in
V&air ,in
pair ,out
V&air ,out
+
+
= g houtlet +
+
air ,in Ainlet 2
air ,out Aoutlet 2
V&
v=
A
inlet
coating pan
outlet

pair ,in
V&air ,in
pair ,out
V&air ,out
+
=
+
air ,in Ainlet 2 air ,out Aoutlet 2
This effect described by Bernoulli

for fluid dynamics is the same effect
found by Vector.
The open cross section of the fully
perforated drum is larger compared
to the partly perforated one. Hence,
the drying is more efficient with the
partly perforated drum.
Case Study (1) Kollicoat IR Carmine

Materials and equipment
Source: Investigating the influence of inlet air temp. and quantity on the maximum spray rate in a side vented pan coater
Cech, Cembali, Funaro, Rottmann, Mistry, Wildschek, et al., 37th CRS World Meeting, July 2010, Portland, U.S.A.
Side vented pan coater

Perfima Lab and Perfima 200
Formulations
Core ingredients
Ludipress LCE
Kollidon VA 64
Mg-Stearate
Coat ingredients
Kollicoat IR Carmine
Water
Quantity [%]
79.5
20.0
3.0
Quantity [%]
25.0
75.0

Trial set up for the perforated drum
Source: Comparing the up scaling characteristics of an instant release coating in solid wall and side vented pan coaters
All parameters in large scale

were adjusted according to the
suggested up scaling strategy
and are based on the process
settings in small scale the
surface quality was found to be
identical in all scales.
Perfima Lab
40 kg
10.9 kg
2
1
7 rpm
9 rpm
(361 mm/s)
(360 mm/s)
Batch size
Number of nozzles
Drum speed
Inlet air temperature 50, 60, 70C

Inlet air quantity
50, 60, 70C
50, 60, 70C
1,060 m/h
2,120 m/h
530 m/h
Perfima 200
140 kg
140 kg
4
4
5 rpm
5 rpm
(349 mm/s)
(349 mm/s)
30, 50, 60,

70C
2,800 m/h

Maximum spray rate found for different scales
Maximum spray rate [g/min]
450
Equipment:
400
Perfima Lab
Perfima 200
350
300
250
200
Coating dispersion:
150
Solid matter content: 25%
100
50
0
0
500
1,000
1,500
2,000
2,500
3,000

30C
50C
60C
70C
It was found that an that as long as high inlet air volumes are used for the
coating process, the inlet air temperature play a secondary role. Actually, an
increase of inlet air temperature did finally not lead to the possibility to
elevate the spray rate.

Summary (1)
Both inlet air quantity and inlet air temperature do influence the maximum
spray rate markedly. However, as temperature is mainly delivering
energy to facilitate the evaporation of the liquid carrier, its effect is
limited. As soon as the energy supply exceeds the energy demand of the
evaporation process, a further increase in temperature does not affect
the spray rate anymore.
Under conditions of an excessive energy supply, the time for evaporating
and exhausting the liquid carrier determines the maximum spray rate.
The time as limiting factor can be influenced by the inlet air volume. An
improvement in drying efficiency can be achieved by an increase in
process air quantity, which is attended by higher air velocity. This
reduces the heat transfer coefficient causing a faster energy transfer.

Summary (2)
The Perfima 200 allows using high process air volumes. This enables the
conduction of coating processes at unusually low inlet air as well as
product temperatures. Especially, if temperature sensitive cores have to
be coated, this characteristic might be an interesting option to be
considered in process optimisation.
Deducing an up scaling strategy

Producing the same quality in different scale
Conditions to produce film coated tablets in different scale with

identical quality and comparable stability:
Energy exposure / core bed temperature
Temperature sensitive drugs
Humidity exposure / spray rate
Water/humidity sensitive drugs
Homogeneity of layer (e.g. thickness)
Functional coating formulations
Obtaining the same dissolution profile
Obtaining the same protective properties


Energies passing the 1st system boundary
Exhaust air
Temperature, quantity, humidity
nd
Convection
sys
.
Q5
.
Q6
tem
bo
un
da
ry
.
Q1
.
Q2
.
Q3
.
Q4
Wt
Inlet air
Dispersion
Temperature, quantity
Compressed air
Atomisation air, pattern air
Light
Electric power
Work
rotation of drum
1st system boundary

Energies passing the 2nd system boundary
Exhaust air
nd
Convection
.
Q5
.
Q6
sys
tem
bo
un
.
Q7
da
ry
Evaporation of liquid carrier

Spray rate
1st system boundary
.
Q1
.
Q2
.
Q3
.
Q4
Wt
.
Q8
Inlet air
Dispersion
Temperature, quantity
Compressed air
Atomisation air, pattern air
Light
Electric power
Work
Rotation of drum
Cores
Temperature, speed
Variable
Constant
Disregarded

Aim for the applied spray rate
Low spray rate

High spray rate Mean spray rate
Range of usable spray rates

Very low spray rates may cause spray drying effects, even if
this is not a problem, with most products a very high
abrasion (friability) and long process times will be found.
Mean spray rates lead to best results with regard to surface
quality. For optimising the process time the highest spray
rate which results in perfectly coated surfaces has to be
evaluated.
AIM
High spray rates bear the risk of overwetting. The likelihood

of rough surfaces is high.

Droplet size
Source: Experiments on the atomization of liquids in an airstream
S. Nukiyama, Y. Tanasawa; Transaction of the Japan Society of Mechanical Engineers; 1939
In any up scaling considerations it is important to keep the nozzle settings

constant. This is for instance droplet speed. Yet droplet size is also of huge
importance and has to be regarded.
DDs
s
Mean
Meandroplet
dropletsize
size
Surface
tension
Surface tensiondispersion
dispersion
Density
dispersion
Density dispersion
[m]
[m]
[N[N/m/ ] ]
m
[kg
[kg/m
/ ]]
m
m
air,liq Ratio
Ratioofofexit
exitspeed
speedair
air: :liquid
liquid [ [m/s/]s]
air,liq
Dyn.
[mPas]
Dyn.viscosity
viscositydispersion
dispersion
[mPas]
JJ
Ratio
of
exit
quantity
air
:
liquid
[-]
Ratio of exit quantity air : liquid [-]
1.5
585 103
1000
0.225
0.45
Ds =

+ 1683 ( )
J
air ,liquid

Circumferential speed
u = dn
u =u
s
d
d
d n = d n
s
n =n
u
us
C. speed small scale
[cm/s]
[cm/s]
ul
C. speed large scale
[cm/s]
d
n
Diameter drum
Pan speed
[cm]
[1/s]
It is aim to keep a constant circumferential velocity.


Calculating tablet velocity
Source: Prediction of tablet velocity in pan coaters for scale-up
Ronny Mller, Peter Kleinebudde; Powder Technology 173 (2007) 51-58
Velocity of particles in a
tumbling blender
or simplified
g
= k r npan
d
2
3
Velocity of particles in a
tumbling blender considering
the filling degree
1
6
g
= k r npan 1.8
d
2
3
2 (2r n )
2u
1
6
k
r
Particle velocity
Constant
Pan radius
[cm/s]
[-]
[cm]
npan
g
Pan speed
Gravity (981)
[1/s]
[cm/s]
Particle size
[cm]
Filling degree
[-]

Process air volume
& production
m
&
Vproduction =
V&pilot
& pilot
m
According to the spray rate, the

inlet air quantity has to be adapted.

Making sure that all products are the same
Keeping the surface time constant

The limiting factor in film coating is the amount of dispersion applied
on a single core when it is passing the spray pattern once.
Keeping the drying / evaporation of the liquid carrier constant

Relative spray rate not calculated on batch size, calculated on
number of assembled nozzles
Keep the same type of nozzle
Keep the same tablet speed by adjusting the circumferential
speed accordingly
Case Study (2) Kollicoat Protect

Schema for the up scaling trial
Number of
nozzles
If the maximum spray rate per

nozzle is determined, the up scaling
calculation will be quite simple.
Spray rate
[kg]
[g/min]
Inlet air
quantity
[m
[m/h]
50
200
2000
100
200
2000
100
300
3000
200
300
3000
200
400
4000
140
9800
120
8400
total process time

[minutes]
To account for the increasing water

impact (increasing overall spray
rate), the inlet air volume has to be
adapted as well.
Batch size
100
7000
80
5600
60
4200
40
2800
20
1400
0
25
75
125
175
inlet air quantity [m/h]
Theoretical scale up calculations
0
225
batch size [kg]

total process time
[minutes]
inlet air quantity

[m/h]

Perfima 200, Kollicoat Protect
Source: Scaling up a Film Coating Process by Keeping the Ratio of Spray Rate and Inlet Air Quantity Constant
Cech, Wildschek; BASF SE; Funaro, Mondelli, Cembali; IMA; ExcipientFest, June 18./19., 2008, Cork, Ireland
Formulations
Drum design
Coat ingredients
Quantity [%]
Kollicoat Protect
Kaolin
Titanium dioxide
Iron oxide (brown)
25.0
67.0
3.0
5.0
Maximum drum load

Perfima 200
Minimum drum load


Schema for the up scaling trial
Trial
Number of
nozzles
Process time [minutes]
Up scaling calculations / results
100
8000
80
6400
60
4800
40
3200
20
1600
0
25
Batch size
[kg]
35
75
75
136
136
Spray rate
[g/min]
200
200
300
300
400
Inlet air
quantity
[m/h]
1,750
1,750
2,625
2,625
3,500
Process
time
[minutes]
31
66
44
79
60
50
75
100
Batch size [kg]

Total process time
[minutes]
125
0
150
Inlet air quantity

[m/h]
For achieving an economical and

fast production scale film coat
process very short process times
have to be realised in small scale.
Case Study (3/1) Kollicoat IR Carmine

Materials and equipment perforated drum
Cech, Cembali, Funaro, Rottmann, Mistry, Wildschek, et al., 37th CRS World Meeting, July 2010, Portland, U.S.A

Perfima Lab and Perfima 200
Formulations
Core ingredients
Ludipress LCE
Kollidon VA 64
Mg-Stearate
Coat ingredients
Water
Quantity [%]
79.5
20.0
3.0
Quantity [%]
25.0
75.0

Trial set up for the perforated drum

Perfima Lab
Perfima 200
40 kg
140 kg
7 rpm (361mm/s)
5 rpm (349 mm/s)
50C
50C
Inlet air quantity
1,060 m/h
2,120 m/h
Maximum spray rate
150 g/min
300 g/min
Batch size
Number of nozzles
Drum speed

Materials and equipment solid wall drum
Cech, Cembali, Funaro, Rottmann, Mistry, Wildschek, et al., 37th CRS World Meeting, July 2010, Portland, U.S.A
Solid wall coater

GS HP 25 and GS 300
Formulations
Core ingredients
Caffeine, gran. 0.2-0.5
Ludipress LCE
Kollidon CL-F
Kollidon VA 64 Fine
Mg-Stearate
Coat ingredients
Water
Quantity [%]
15.5
74.0
5.0
5.0
0.5
Quantity [%]
25.0
75.0

Trial set up for the solid wall drum

GS HP 25
GS 300
22 kg
202 kg
8 rpm (335 mm/s)
4 rpm (329 mm/s)
60C
60C
Inlet air quantity
350 m/h
1,400 m/h
Maximum spray rate
48 g/min
192 g/min
Batch size
Number of nozzles
Drum speed
Case Study (4) Kollicoat SR 30 D

Materials and equipment
Source: Investigating the up scaling properties of a sustained release coating using side vented pan coating technology
T. Agnese, T. Cech, F. Wildschek, C. Funaro, G. Mondelli, F. Cembali, PBP World Meeting, March 2010, Valetta, Malta
Formulations
Core ingredients
Quantity [%]
Caffein, gran. 0.2-0.5

Ludipress LCE
Kollidon CL-F
Kollidon VA64 fine
Mg-stearate

Perfima Lab
15.5
74.0
5.0
5.0
0.5
Coat ingredients
Quantity [%]
Kollicoat SR30 D
Triacetin
Kollicoat IR
Kollidon 30
Titanium dioxide
Iron oxide red
Talc
Water
43.5
0.7
3.3
0.5
0.5
0.5
3.5
47.5
Drum
Small
Medium
Large
Diameter
[mm]
Volume
[L]
Drum speed
[s-1]
765
865
985
15
30
60
9
8
7

Coating and analytical results
1.0
Round shaped cores

S
M
L
21.8
43.7
600
600
1,200
39
39
78
0.6
Small pan
Medium pan
Large pan
0.4
0.2
0.0
0
Football shaped cores

S
M
L
Batch size
[kg]
Inlet air volume
[m/h]
Number of
nozzles
Spray rate
[mL/min]
Drug release [-]
10.9
10.1
40.3
530
1,060
31
62
12
16
20
24
Dissolution time [h]

1.0
0.8
Drug release [-]
Batch size
[kg]
Inlet air volume
[m/h]
Number of
nozzles
Spray rate
[mL/min]
0.8
0.6
Small pan
Large pan
0.4
0.2
0.0
0
12
16
20
24
Dissolution test: 0.08M HCl (pH 1.1, 2h), phosphate buffer (pH 6.8, 22h)

Considering the standard deviation of the dissolution profiles
Round shaped cores

S
M
L
Batch size
[kg]
Inlet air volume
[m/h]
Number of
nozzles
Spray rate
[mL/min]
10.9
21.8
43.7
600
600
1,200
39
39
77
The necessarily to apply the coating

material with the maximum possible
spray rate led to very short process
times in small scale (72 min., 11kg).
These caused a high standard
deviation for the small pan.
Drug release [-]
1.0
0.8
Small pan
Medium pan
Large pan
0.6
0.4
0.2
0.0
0
12
16
20
24


Football shaped cores

S
M
L
Batch size
[kg]
Inlet air volume
[m/h]
Number of
nozzles
Spray rate
[mL/min]
10.1
40.3
530
1,060
31
62
Due to the tablet shape, lower spray

rates had to be applied for these
cores, leading to a longer process
time (80min., 10kg), hereby causing
a lower standard deviation in the
small pan.
Drug release [-]
1.0
0.8
Small pan
Medium pan
Large pan
0.6
0.4
0.2
0.0
0
12
16
20
24


Source: Els Mehuys, Jean Paul Remon, Lab of Pharmaceutical Technology, Ghent University, Gent, Belgium
Round shaped cores

S
L
Coating
Batch size
[kg]
Inlet air volume
[m/h]
Number of
nozzles
Spray rate
[mL/min]
10.9
43.7
600
1,200
1.0
0.8
0.6
0.4
39
0.2
0.0
0
12
16
20
24
20
24
D is s o lutio n tim e [h]
77
1.0
Dissolution
Colour (chart)
Samples
S
red
78
0.8
L
blue
80
0.6
0.4
0.2
The coating uniformity represented

by the variations in drug release in
drug release was found to be
improving with larger batch sizes.
0.0
0
12
16
D is s o lutio n tim e [h]
VanKel VK7010 dissolution apparatus equipped with
VK8000 auto-sampler and VK750D heater
How to proceed in an up scaling process?

Use of the up scaling strategy
Feasibility
0.1
Lab
Pilot
15
Production
75
125
500 [kg]
Model 970/S35
Model 970/S75
Model 930/S45
The up scaling strategy applies on processes conducted in lab, pilot and

production scale. Feasibility studies can hardly be basis for up scaling
calculation, problems: dimensional ratios, nozzle, etc.

Development and up scaling start in production
Production scale
Evaluate:
Max. inlet air temp.

Max. inlet air quantity
Number of nozzles
Type of nozzles
Production scale
Lab and pilot scale
Development on:
Formulation (coating, core)
Polymer
Solid matter content
Process parameters
Inlet air temp. and quantity
Spray rate per nozzle
Drum speed
Production, keeping:
Temperatures
Rel. inlet air quantity
Spray rate per nozzle
Number of nozzles
Type of nozzles

Summary (1)
It can be concluded that the up scaling theory suggested for instant

release film coating polymers can be transferred to functional coatings as
well.
As the approach requires very short process times in small scale, the
resulting release profile shows high standard deviation.
The determination of the maximum spray rate in small scale is necessary
to calculate the spray rate and process air volume in large scale, while
maintaining the same moisture exposure throughout the entire scale up
process.

Summary (2)
It is suggested to perform both trials in small scale during development:

1. Using optimal process time with low spray rate to apply a
homogenous coat.
Development of the release profile.
2. Using maximum spray rate to do the up scaling calculations and to
expose the same amount of moisture as in production.
Important for moisture sensitive drugs or formulations.
The energy exposure can easily be kept constant by leaving the cores in
the drum for the required period of time.
Summary
Theoretical consideration
If a certain amount of inlet air is reached, a further increase of process air

quantity does not improve the drying characteristics significantly. The
improvement of the coating process which can be observed, results from
a higher air velocity leading to a higher heat transfer coefficient.
As parameter to calculate a scale-up process, the amount of film coating
dispersion applied on a single core, when it is passing the spray pattern,
can be used.
To simulate the characteristics of a production scale film coating process,
the shortest possible process times has to be used in pilot scale.
Summary
Study 1 keeping the ratio of spray rate and air quantity
Independent from scale, the ratio of spray rate to inlet air volume is
responsible for the surface quality. Using this parameter scale-up
calculation can be done easily.
Process times in small scale have to be as short as possible to be
comparable with large scale.
The Perfima 200 is a variable coater system enabling a broad range of
batch sizes.
Kollicoat Protect can be used with a very low polymer content of just 25%
in pilot and production scale. This enables formulations offering highest
protective properties against ambient moisture.
Summary
Study 2 keeping the ratio of spray rate and air quantity
Source: Investigating the Dependency of the Maximum Spray Rate on the Amount of Inlet Air
The drying efficiency depends strongly on the inlet air quantity. The
higher the inlet air quantity the higher the applicable spray rate.
With very high spray rates process times can be realised which might too
short to assure a uniform coating depending on the mixing efficiency of
the coater.
ExAct magazine
Column on trouble shooting
#21: Film coating Scuffing

#22: Film coating Spots
#23: Tabletting Loss on drying
#24: Film coating Sedimentation
#25: Film coating Plasticizers
to be continued
http://www.pharma-ingredients.basf.com/exact.aspx
Contact
Thorsten Cech
Manager
European Pharma Application Lab
BASF SE
G-ENP/ET Nutrition & Health
Europe, Africa, West Asia
Phone:
Mobile:
Fax:
+ 49 (0) 621 / 60 99 290

+ 49 (0) 173 / 347 99 58
+ 49 (0) 621 / 60 66 99 290
Mail:
Internet:
thorsten.cech@basf.com
www.pharma-ingredients.basf.com
http://www.excipients-academy.basf.eu/Home.aspx

4.basf - 855 - e 17 (TC) - Ima Spain - Up Scalin

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Scaling up

The up-scaling problem

Inlet air quantity

Inlet air temperature

Nutrition & Health Division

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 2

The up-scaling problem

Exhaust air temperature [C]

Rel. spray rate

Rel. inlet air quantity[m/h/kg]

These trials show the

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 3

The up-scaling problem

Process air quantity [m/h]

Spray rate [g/min]

The chart displays the

Batch size [kg]

Commonly used process air quantity

This chart shows the non-linear reality.

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 4

The up-scaling problem

Process air quantity [m/h]

Spray rate [g/min]

The chart displays the

Batch size [kg]

Commonly used process air quantity

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 5

The up-scaling problem

Nutrition & Health Division

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 6

The coating process in different scales

Nutrition & Health Division

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 7

The coating process in different scales

The Process-Parameter-Chart can be considered as perfect tool to

Nutrition & Health Division

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 8

The film coating process

Design (e.g. ABC)

Nutrition & Health Division

Type (e.g. solid)

Pharma Ingredients & Services

The film coating process

Film building process

Droplets of the film coating dispersion

Finally formed filmed

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 10

The film coating process

Time of process cycle

Steady state core bed temperature

Pharma Ingredients & Services

T. Cech - G-ENP/ET - page 11

The film coating process

Process air temperature and humidity

Time of process air in the process