March 2012

C. Funaro, G. Mondelli, F. Cembali

IMA s.p.a. Active Division
M. Di Sabatino, B. Albertini, N. Passerini
Universit degli Studi di Bologna, Dipartimento di Scienze Farmaceutiche
Sugar Coating Process
A study of time-saving and
up-scaling challenges
p. 1 Sugar Coating Process - A study of time-saving and up-scaling challenges
depending upon the formula
and kind of equipment.
For these reasons, sugar coat-
ing is not the frst choice of
technology for pharmaceuti-
cal companies when develo-
ping new drugs.
Our challenge is to reduce
the time required for the
sugar coating process so that
it matches that of flm coat-
ing technology.
In addition, we must fnd a
way to eliminate depen-
dency on operator skills.
The aim of reducing the pro-
cess time to under 5 hours
was achieved as a result of
very effcient equipment and
optimised operating parame-
ters.
The results demonstrated
that the sugar coating pro-
cess can be a cost-effective
technology when following
an optimized procedure on
fully automated equipment.
Moreover, the use of high-
level technology means the
sugar-coating results depend
less operator skill.
Introduction
Aim of the
study
Conclusion
The aim of this study was to
optimize the sugar coating
formula in order to reduce
the number of steps requir-
ed, and as a consequence
to shorten the process time.
This frst batch was proces-
sed on a pilot-scale solid-
wall pan coater, providing a
high level of automation.
Next, the process was up-
scaled in an attempt to main-
tain the same tablet quality
using an automatic procedu-
re within an acceptable pro-
cess time.
Sugar coating is a multi-step
process that increases target
weight by 50% to 100% in
the following phases: sealing,
sub-coating, smoothing,
colouring and polishing.
The main disadvantages
of the sugar-coating process
are the duration of the pro-
cess and the intensive labour
and attention required of
operators. The total process
time can vary from several
days to less than 8 hours
p. 2 Sugar Coating Process - A study of time-saving and up-scaling challenges
Equipment

Solid-wall coating pans were
used on both pilot and pro-
Coating methods
Sealing was achieved by me-
ans of a continuous flm coating
process using Opaglos clear,
until a weight increase of 1%
was achieved.
Sub coating, smoothing
and colouring phases were
performed by repeating the
corresponding suspension
spraying, mixing and drying
phases in sequence (about 50
cycles for pilot tests and about
65 cycles for production tests),
Figure 1: solid wall pan and mixing baffes
until a total weight increase
of 75% was achieved.
Each phase was performed
using different kinds and
amounts of sprayed suspen-
sion, as well as different mixing
times and drying conditions.
In the trials conducted wi-
thout the smoothing suspen-
sion, the smoothing phase was
performed using the colouring
suspension. The polishing
phase was performed by adding
1 g of Carnauba wax powder
for each kg of starting cores
and rotating the tablets at the
highest pan speed.
Coating quality
assessment
Coating quality was evaluated
by visual inspection and by
Scanning Electron Microscope
images (ESEM FEI QUAN-
TA 200) in order to check the
surface for any defects such as
stickiness or roughness.
duction scales. The two pie-
ces of equipment (IMA GS 25
liters and IMA GS 450 liters)
provided mixing baffes (fgure
1), suspension dosing devices
and drying systems of the same
design to maintain geome-
tric similarity. The batch size
was 15 kg for the pilot unit and
250 kg for production scale.
Materials

Round-shape placebo tablets
(Lactose Spray dried 60%, Avicel
pH 102 39%, Magnesium Stea-
rate 1%) with a mean weight of
280 mg, mean diameter of 9 mm
and mean crushing strength of
90 N were used as a substrate
for the sugar coating process.
Opaglos clear (Colorcon, Dart-
ford, UK) was used as the flm
coating agent for sealing. Opalux
Brown (Colorcon, Dartford, UK),
sugar, talc, Arabic gum, titanium
dioxide and calcium carbon-
ate (Polichimica, Bologna, Italy)
were utilised in the preparation
of sugar coating suspensions,
kept at 70C or 50C for sub
coating and 55C for smoothing
and colouring. Carnauba wax
(Polichimica, Bologna, Italy) was
used in the fnal polishing step.
Experiment
p. 3 Sugar Coating Process - A study of time-saving and up-scaling challenges
Result and
discussion
Pilot scale
STEP
Pan
speed
(rpm)
8
9-12
9-12
9-12
12
Intel T
(C)
60
60-65
60-65
60-65
na
Spray
time
(sec)
Mix
time
(sec)
Dry
time
(sec)
Cores
T
(C)
3-10
3-10
3-10
na
600
120-150
120-150
120-150
600
120-150
120-150
120-150
na
35
38-35
38-35
38-35
na
Sealing
Sub coat
Smoothing
Coloring
Polishing
All steps were performed using 250 m
3
/h as inlet air quantity,
-20 Pa as negative pressure, spray pressure 1,6 bar, recycling pressure 1
bar, spray pattern 70, 1 gun, nozzle diameter 1mm, gun distance 20 cm.
Sub coating suspension was kept at 70.
Total process time 5 hours.
of 4.5 hours was achieved
by eliminating the smoothing
suspension (performing the
smoothing phase with color-
ing syrup) and decreasing the
mixing time and the drying time
to 2 minutes each.

The frst batch was processed on
the pilot unit with the purpose
of reducing the process time
below 6 hours using the tradi-
tional sugar coating procedure.
After the preliminary trials, an
optimal combination of oper-
ating parameters that yield-
ed good-quality coating was
found. These parameters are
reported in following table.
The aim of keeping the process
time below 5 hours was achie-
ved through the combination
of very effcient equipment and
the optimisation of operating
parameters.
Parameters for traditional sugar coating procedure (pilot batch)
The possibility of a further re-
duction in total process time
while maintaining the level of
sugar coating quality was eval-
uated by modifying both the for-
mulation and the operating pa-
rameters. A total process time
Cross section of pilot and production batches
at different coating steps
600 600
Sealing Sub-coat Smooth/Color
p. 4 Sugar Coating Process - A study of time-saving and up-scaling challenges
Moreover, an improvement in
drying conditions was neces-
sary: the inlet air volume was
increased from 250 m
3
/h to
270 m
3
/h and the inlet air
temperature was increased
from 60-65C to 65-70C in the
sub-coating step.
SEM images show evidence of
the formation of a sandwich
edge during the sub-coating
step, which was then comp-
letely flled by the subsequent
smoothing/coloring step;
the fnal sugar coated product
revealed an absence of any
coating defects.
Production scale
The optimized formula and
operating parameters achieved
on pilot equipment was applied
to the subsequent up-scaling
phase aimed at maintaining
STEP
Pan
speed
(rpm)
6
6-8
6-8
6-8
10
Intel T
(C)
60
70-60
70-60
70-60
na
Spray
time
(sec)
Mix
time
(sec)
Dry
time
(sec)
Cores
T
(C)
10-70
10-70
10-70
na
1800
120-90
120-90
120-90
900
120-150
120-150
120-150
na
35
38-30
38-30
38-30
na
Sealing
Sub coat
Smoothing
Coloring
Polishing
All steps were performed using 2000 m
3
/h as inlet air quantity,
-20 Pa as negative pressure, spray pressure 2 bar, recycling pressure 1
bar, spray pattern 80, 1 gun, nozzle diameter 1,5 mm, gun distance 25 cm.
Sub coating suspension was kept at 70.
Total process time 8 hours.
good-quality coating and a short
process time. Reproducibility
was also taken into considera-
tion. The operating parameters
used for the frst production
batch are reported in following
table. Although these reported
parameters resulted in good-
quality coating, the process
time was too long (8 hours).
To improve the process time
in production scale, the second
batch was processed with an
increased spray time (80 se
conds) and a reduced mixing
time (1 minute) during the
sub-coating step. The overall
process time was thus reduced
to 7 hours, but the resulting
coating surface was rough.
The third batch was performed
under the same conditions as
the second, with the exception
of the spray pressure which
was increased to 2.5 bar for
greater spray quantity and
the temperature of the sub-
coating suspension which
was kept at 50C to improve
the coating surface.
The result was very good in
terms of both process time
(6 hours) and coating quality.
The fourth production batch
was performed under the same
conditions as the previous one,
achieving good-quality co-
ating in 6 hours of process
time and demonstrating repro-
ducibility. SEM images of the
fourth production batch show-
ed behavior that was identical
to the pilot batch.
1800 1800