Film Coating: Scuffing - Pharma Ingredients & Services BASF

Excipients & Actives for Pharma | No. 21, October 2008
Dear Reader,
Time-to-market is becoming increasingly
important for pharmaceutical companies.
The faster a new product is introduced onto
the market, the longer the originator benefits
from its development due to the remaining
patent-protection period. Speed is also of
the essence for producers of generics, as
the first-to-market strategy ensures a high
market share. On the other hand, regulatory
authorities and in-house guidelines call for
ever more detailed and time-consuming
documentation.
Fulfilling both these
requirements reduces
the time available for
optimizing formulations
and processes within
the scope of ongoing
projects. Obstacles
encountered during in
the formulation phase
Thorsten Cech
frequently lead to time
Manager, European Pharma
pressure. Concessions
Application Lab
are required to make
up for lost time. In daily work a great deal
of a valuable time is needed to solve minor
problems that arise during routine processes
like granulation, tableting and coating.
This is where BASF comes in. To investigate
the performance of our excipients, we continuously
conduct trials involving various
pharmaceutical technologies. We not only
“…we provide
you with expert
develop numerous
advice on how
generic drug formulations,
but also run
to improve the
quality and efficiency
of your
processes under different
conditions. Borderline
processes are development and
of particular interest manufacturing
to us, as they help us processes”
to better understand
the performance of our products. Furthermore,
close relationships with a number of
manufacturers of pharmaceutical technologies,
and regular exchange of ideas and
experience enable us to act on our findings.
By gathering and appraising all this information,
we provide you with expert advice on
how to improve the quality and efficiency of
your development and manufacturing
processes.
This edition of ExAct sees the launch of our
new Troubleshooting column. In the following
issues, we plan to discuss a specific problem
and its solution. We hope this will support you
in your your daily work and help you gain
valuable time.
Yours sincerely,
Thorsten Cech
Manager, European Pharma Application Lab
Contents
Plasticizers – Influence of Plasticizer on
Film Properties
Pages 2-5
Kollicoat ® – Reliability of Drug Delivery
Systems
Pages 6-8
Propylene Glycol – Implementation of
GMP Standard
Page 9
Troubleshooting – Film Coating: Scuffing
Pages 10-12
News:
– Kollicoat IR: Draft Monograph for the
European Pharmacopoeia
– USP: Pharmaceutical Ingredient
Verification Program
– Regulatory affairs
Page 13
Workshops Page 14
New Media:
– Booklet: Pharmaceutical Technology of
BASF Excipients
– Ludipress ® Brochure
– Kollicoat Poster
Page 15
Imprint
Publisher: BASF SE
Editorial staff: Michael Black, Suzanna Brown,
Thorsten Cech, Hubertus Folttmann, Bernd Fussnegger,
Felicitas Guth, Philipp Hebestreit, Karl
Kolter, Kathrin Meyer-Boehm, Sascha Opaska, Inge
Rademacher, Claudia Schneider, Florian Wildschek
Concept/layout:
Château Louis Strategische Markenführung und
Kommunikation GmbH
Print:
Grosch! Druckzentrum, Druck- und Verlags- GmbH
Preview:
Melt Extrusion for
Pharmaceuticals
Calendar
Contact Page 16
Trademarks are owned by BASF SE

Excipients & Actives for Pharma
Influence of Plasticizers on the Film Properties of
HPMC and PVA and Comparison of the Results with the
Properties of Kollicoat ® IR as a single Film Former
By Thorsten Cech 1 (thorsten.cech@basf.com), Karl Kolter 2 (karl.kolter@basf.com)
1
BASF SE, European Pharma Application Lab, 67056 Ludwigshafen, Germany
2
BASF SE, Development Pharma Ingredients, 67056 Ludwigshafen, Germany
INTRODUCTION
In the field of instant release
film coating a wide range of
film forming polymers can be
used. Even if the application
is the same, the film forming
characteristics of the polymers
hydroxy propyl methylcellulose
(HPMC), polyvinyl alcohol (PVA)
and Kollicoat IR are completely
different [1]. HPMC 3mPas is a
very brittle film former, whereas
PVA was found to be extremely
supple. In contrast, Kollicoat IR
offers a broad range of usable
process parameter settings.
To improve the application properties
of HPMC and PVA additional
excipients have to be
added to the formulation, among
them plasticizers.
OBJECTIVE
This paper aims to investigate
the influence of plasticizers on
the film-coating properties of
HPMC 3mPas and PVA. Since
Kollicoat IR was found to form
stable film without any additives,
for example plasticizers, this
product is used by itself as a
reference.
Of particular interest were the
changes in water vapor transmission
rate (WVTR) and elongation
at break.
EXPERIMENTAL
Materials
Table 1 shows the formulations
tested regarding their WVTR and
their elongation properties.
For the film coating trials, HPMC
3mPas and PVA in combination
with 10% PEG 6000 were used.
Equipment
Film Caster: Coatmaster, Erichsen
Testing Equipment (Germany);
Transmission Tester: Permatran,
Mocon (USA);
Texture Analyser: TA-XT2i HR,
Stable Micro Systems (UK);
Drum Coater: AccelaCota 24”,
Manesty (UK)
Methods
The parameters of comparison
were the following:
Viscosity of the polymer
solution
(25°C, w/w = 20%)
Elongation at break
(at 23°C/54 % r.h.)
Water vapor transmission
rate [3]
(23°C/0% r.h. – 23°C/85% r.h.)
Coating parameters
without plasticizer and
with 10% PEG 6000 added
Table 1: Formulations tested
Table 2: Viscosity and Elongation at Break of the Polymers without
additional Plasticizers
Polymer Plasticizer Quantity [%]
Polymer Viscosity [mPas] Elongation at break [%]
Kollicoat IR non –
HPMC 3mPas propylene glycol (PG) 5, 10, 20, 40
propylene glycol (PEG) 400 10, 20, 40
propylene glycol (PEG) 6000 5
triacetin (TAC) 5, 10, 20, 40
triethyl citrate (TEC) 5, 10, 20, 40
PVA propylene glycol (PG) 5, 10, 20, 40
propylene glycol (PEG) 400 5, 10, 20, 40
propylene glycol (PEG) 6000 5, 10, 20
Kollicoat IR 91 169
HPMC 3mPas 561 4
PVA 590 226

No. 21, October 2008 | PAGE 3
Due to the brittleness of some
cast films containing PEG 6000,
not all formulations could be prepared.
Furthermore, the lipophilic
plasticizers TEC and TAC could
not be used in the combination
with PVA. A separation of the
plasticizer was observed.
to have a very high elasticity,
whereas HPMC 3mPas was brittle
and therefore low in elongation
at break (Table 2).
The change in elongation at
break when different quantities
of plasticizer were added was
determined.
RESULTS
Viscosity
HPMC 3mPas and PVA were found
with quite similar viscosities of its
polymer solutions (w/w = 20%).
With nearly 600 mPas, the solutions
tested could hardly be used
as coating solution. Kollicoat ® IR
showed significant flow properties
(Table 2). With less than 100
mPas, the solution is still easily
usable for film coating processes.
Elongation at Break
PVA and Kollicoat IR were found
Surprisingly, the influence of
plasticizers on the elongation at
break was quite low. Compared
to the properties of the polymer
itself, elasticity increased just
slightly with relevant plasticizer
contents.
Just with 40% plasticizer added,
a significant increase in elongation
at break could be determined
(Figure 1 and 2).
The determination clearly showed
that the elongation prop erties
Elongation at break test equipment: Texture Analyser, TA-XT2i HR, Stable Micro Systems
could not be influenced by Water Vapor Transmission
adding plasticizer. Therefore, if Rate (WVTR)
cracks in the applied film occur There is an ongoing discussion if
during storage, additional plasticizer
cannot prevent this effect. vapor transmission. The
plasticizers support the water
tested
Figure 1 – Elongation at break of PVA as function of plasticizer and
plasticizer content
Figure 2 – Elongation at break of PVA as function of plasticizer and
plasticizer content
15.0
elongation at break [%]
450
elongation at break [%]
12.5
10.0
PG
PEG 400
PEG 6000
TAC
TEC
400
350
PG
PEG 400
PEG 6000
TAC
TEC
7.5
300
5.0
250
2.5
200
0.0
150
O 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
plasticizer content [%]
O 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
plasticizer content [%]

Excipients & Actives for Pharma
CONCLUSIONS
polymers can be used as a base
for moisture-protective coatings.
Therefore, it was useful to determine
the WVTR, even if the main
protection depends on the
amount of pigments contained in
the film formulation [2].
In this study, trials were carried
out to determine the influence of
plasticizers on the WVTR [3]. The
WVTR was found to be lower
with relevant plasticizer contents.
Plasticizer used in a ratio of up
to 20% supported the protective
properties of the tested films
(Figure 3 and 4).
Coating Properties
The coating properties were
determined by using Process-
Parameter-Charts [4].
HPMC 3 mPas was found to be
a brittle film former. A product
temperature above 43–45°C
caused defects in the film surface
(Figure 5). Adding PEG
6000 improved the coating properties
significantly (Figure 6).
PVA, on the contrary, was found
to be a very supple film former.
As water acts as a plasticizer,
coating was only possible under
very dry conditions (low spray
rate, high product temperature)
(Figure 7). The addition of PEG
6000 improved the coating properties
of PVA as well (Figure 8).
Just in this case, PEG 6000
worked very differently, as it is
not acting as a plasticizer. Having
a molecular weight of about
6000 Daltons PEG 6000 is a brittle
film former in its own right.
By mixing PVA with PEG 6000
the properties of the two film
Kollicoat ® IR offers the lowest dynamic viscosity, enabling high
solid matter contents and short process times.
The elongation properties of HPMC 3mPas can hardly be
improved by adding various plasticizers.
WVTR can be reduced slightly by adding some plasticizer.
Adding PEG 6000 to a HPMC-3mPas-based formulation reduces
the brittleness of the film (the film becomes foldable)
without improving its elasticity (or flexibility which is responsible
for potential cracks in the applied film).
As PEG 6000 decreases the brittleness of the formed polymer
film, the coating properties of HPMC 3mPas can be improved
significantly.
The coating properties of PVA can be improved significantly by
adding PEG 6000.
Kollicoat IR has far superior coating properties.
formers were combined. Hence,
the coating properties were
improved.
However, the characteristics of
the two polymers could be positively
influenced by adding plasticizers
like PEG, the coating
results with Kollicoat IR still
remained better (Figure 9).
Figure 3 – WVTR of HPMC 3mPas as function of plasticizer and plasticizer
content
Figure 4 – WVTR of PVA as function of plasticizer and plasticizer content
1000
elongation at break [%]
1000
elongation at break [%]
900
800
700
600
PG
PEG 400
PEG 6000
TAC
TEC
900
800
700
600
PG
PEG 400
PEG 6000
TAC
TEC
500
500
400
400
300
300
200
200
100
100
0
0
O 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
O 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0
plasticizer content [%]
plasticizer content [%]

No. 21, October 2008 | PAGE 5
Figure 5 – Process-parameter-chart of HPMC 3mPas
Figure 6 – Process-parameter-chart of HPMC 3mPas, 10% PEG 6000 added
50
45
40
35
product temperature [°C]
50
45
40
35
product temperature [°C]
30
30
25
25
20
20
25 75 125 175 225 275
total process time [min]
15
25 75 125 175 225 275
total process time [min]
15
Figure 7 – Process-parameter-chart of PVA
Figure 8 – Process-parameter-chart of PVA, 10% PEG 6000 added
50
45
40
35
product temperature [°C]
50
45
40
35
product temperature [°C]
30
30
25
25
20
20
25 75 125 175 225 275
total process time [min]
15
25 75 125 175 225 275
total process time [min]
15
Figure 9 – Process-parameter-chart of Kollicoat ® IR
50
45
40
35
30
25
20
product temperature [°C]
REFERENCES
[1] T. Cech, K. Kolter; Comparison of the Coating Properties of Kollicoat ® IR and other
Film Forming Polymers Used for Instant Release Film-Coating, ExcipientFest
Europe, June 19.-20., 2007, Cork, Ireland,
[2] T. Cech, K. Kolter; Developing an Instant Release Moisture Protective Coating Formulation
based on Kollicoat ® Protect as Film Forming Polymer; PBP World Meeting 2008
[3] ASTM F-1249
[4] T. Cech, K. Kolter; Comparison of the Coating Properties of Instant Release Film
Coating Materials Using a Newly Developed Test Method – the Process-Parameter-
Chart, PSWC 2007
Published in ExcipientFest Europe, June 17.-18., 2008, Cork, Ireland, G-EMP/MD
25 75 125 175 225 275
total process time [min]
15

Excipients & Actives for Pharma
Reliability of Drug Release from Innovative Single-Unit
Kollicoat ® Drug Delivery Systems
K. Meyer-Boehm and K. Kolter (karl.kolter@basf.com)
BASF SE, R&D Project Management Excipients, 67056 Ludwigshafen, Germany
ABSTRACT/SUMMARY
Sustained-release characteristics
as well as the influence of
mechanical stress on the new
single-unit Kollicoat DDS was
investigated. The delivery system
showed a reliable release profile,
a self-repair mechanism and
bursting forces of the swollen
system greatly exceeding the
maximum contraction strength in
the human stomach and intestine.
Thus, dose dumping should
not be a risk.
INTRODUCTION
In the past, there was only one
coated single-unit drug delivery
system available, which was
quite complex and difficult to
produce, the OROS-system [1].
Mainly the risk of dose dumping
prohibited the development of
other systems. Recently, innovative
single-unit drug delivery
systems have been developed,
releasing the drug by diffusion
through a membrane. These
sustained-release dosage forms
are produced by coating a tablet
core with a combination of very
flexible hydrophilic (Kollicoat IR)
and lipophilic (Kollicoat SR 30 D)
polymers [2]. This combination
does not require organic solvents
and produces a strong sustained-release
effect.
Generally, due to the structure
and the principle of release there
might be the risk of dose dumping.
Therefore, the safety and
mechanical stability of this
dosage form was investigated
using pseudophedrine HCl as
model drug.
EXPERIMENTAL METHODS
Immediate release pseudo ephe -
drine HCl cores (9mm diameter)
were manufactured by blending
all ingredients for 10 min in a turbula
mixer and direct compression
on a Korsch PH 106 rotary
press at 10 kN compression
force.
Coating was performed in a 24”
Accela Cota perforated pan
coater.
Dissolution was determined in
paddle equipment with 0.08N
HCl for 2h and a subsequent
pH-change with phosphate
buffer to pH 6.8 at a stirring
speed of 50 rpm.
Table 1: Composition of pseudoephedrine
cores
Ingredient
[mg]
Pseudoephedrine HCI 120.0
Ludipress ® 274.0
Aerosil ® 200 2.0
Magnesium stearate 4.0
Total 400.00
Table 2: Coating composition
SR : IR
7 : 3 8 : 2
[%] [%]
Kollicoat SR 30 D 37.77 43.17
(polyvinyl acetate 30% dispersion, BASF)
Kollicoat IR 4.86 3.24
(polyvinyl aclohol-polyethylene glycol graft copolymer, BASF)
Triacetin 1.62 1.62
Talc 4.05 4.05
Water 51.70 47.92
Total 100.0 100.0
Table 3: Coating parameters
Inlet air temperature 60° C
Outlet air temperature 35° C
Spraying rate
32 g/min
Atomizing pressure 1.5 bar
Nozzle
1.0 mm

No. 21, October 2008 | PAGE 7
0 min 90 min 210 min
Mechanical stability of swollen
tablets after various release
times was tested using a Texture
Analyzer (TA-XT2 HiR; Stable
Micro Systems). The force
required to burst the coating was
calculated from force-displacement
curves.
260 min 480 min 960 min
Furthermore, dissolution as well
as mechanical stability of the
Kollicoat ® DDS after pricking the
coating with a needle was investigated.
RESULTS AND
DISCUSSION
The sustained-release coating
could be applied easily and the
resulting film-coated tablets displayed
a smooth homogeneous
surface. When put into the dissolution
medium, water permeates
through the membrane and
dissolves the active, enabling it
to diffuse to the outside. The
Figure 1: Behavior of the single unit DDS in dissolution
decisive property of the coating coating level should not be lower
is its flexibility, because it has to than 12mg/cm 2 . Pricking the
withstand the swelling of the coating with a needle prior to the
core without cracking (Figure 1). dissolution did not have any
The dissolution studies (Figure 2) influence on the release rate,
show that the release rate can demonstrating that the slight
be slowed down by increasing swelling of the polyvinyl acetate
the coating thickness and the in water closes the hole (selfrepair
mechanism).
ratio of Kollicoat SR 30 D : Kollicoat
IR. In parallel, the lag-time
was prolonged due to a slower After a few hours in the dissolution
tester the tablets look like
permeation of water through the
coating into the core. In order to water-filled balloons. However,
guarantee a homogeneous coating
and a reliable release, the atively high forces. When
these balloons can withstand rel-
tested
in a Texture Analyzer the swollen
tablets are compressed and the
force increases exponentially to
a certain value, where the coating
bursts and the force drops
immediately (Figure 3).
Figure 2: Dissolution of pseudoephedrine – Kollicoat DDS
Figure 3: Force-displacement curve of a swollen Kollicoat DDS
dissolution [%]
120
100
80
60
40
force [N]
40
35
30
25
20
15
20
0
SR/IR 7:3; 12 mg/cm 2
SR/IR 7:3; 12 mg/cm 2 needle pricking
SR/KIR 8:3; 16 mg/cm 2
O 2 4 6 8 10 12 14 16 18 20 22 24
time [h]
10
5
0
O 2
4
6 8
displacement [mm]

Excipients & Actives for Pharma
When the bursting force was put
as a function of dissolution time it
stayed almost constant until 14h
to 18h at high levels of approx.
35N in case of the SR/IR 7:3,
12 mg/cm² coating and 50N in
case of the SR/IR 8:2, 16 mg/cm²
coating. The higher value of the
latter combination reflects the
thicker coating. At the end of
dis solution the force slightly
decreased but did not fall below
15N. As expected, displacement
changed parallel to force. Within
the first hours of dissolution,
exact bursting forces could not
be determined due to hard, not
completely hydrated cores
(Figure 4 and 5).
Pricking the coating with a needle
prior to dissolution led to the same
bursting force at the beginning,
but it was earlier and more strongly
reduced upon dissolution time.
However, after 24h still almost
10N were recorded (Figure 6).
From the literature [3,4], it is
known that the maximum contraction
strength is around 1.9N
in the stomach and 1.2N in the
small intestine. These forces
should be tolerated by the
described Kollicoat ® DDS without
any damage.
REFERENCES
[1] J.A. Cardinal, Controlled release
osmotic drug delivery systems for oral
applications, Transport Processes in
Pharmaceutical Systems, Marcel
Dekker Inc. 2000, 411-444.
[2] K. Kolter and S. Gebert, Proceedings
of the 4th World Meeting on Pharmaceutics,
Biopharmaceutics and Pharmaceutical
Technology, 8-11th April
2002, Florence, 137 (2002).
[3] M. Kamba, Y. Seta, A. Kusai, M. Ikeda
and K. Nishimura, Int. J. Pharm. 2000
(208), 61-70 (2000).
[4] M. Kamba, Y. Seta, A. Kusai and K.
Nishimura, Int. J. Pharm. 2002 (237),
139-149 (2002).
G-EMP/MD234
Figure 4: Bursting force of swollen Kollicoat DDS (SR/IR 7:3; 12 mg/cm²
as a function of dissolution time
45
40
35
30
25
20
15
10
5
0
bursting force [N]
force [N]
displacement [mm]
displacement [mm]
O 2 4 6 8 10 12 14 16 18 20 22 24
dissolution time [h]
Figure 5: Bursting force of swollen Kollicoat DDS (SR/IR 8:2; 16 mg/cm²)
as a function of dissolution time
60
50
40
30
20
10
bursting force [N]
force [N]
displacement [mm]
displacement [mm]
7
6
5
4
3
2
1
0
7
6
5
4
3
2
1
0
0
O 2 4 6 8 10 12 14 16 18 20 22 24
dissolution time [h]
CONCLUSION
A new innovative single-unit drug delivery system with zero
order release kinetics was developed by aqueous coating of
immediate release cores.
A combination of extremely flexible lipophilic and hydrophilic
polymers (Kollicoat SR 30 D and Kollicoat IR) allows simple
and reliable manufacture of this DDS without the risk of dose
dumping.
Drug release from the Kollicoat DDS can be adjusted by varying
the coating thickness and lipophilic-hydrophilic polymer
ratio (SR:IR).
Within the release period single-unit Kollicoat DDS exhibits a
mechanical stability far higher than the maximum contraction
forces in the human stomach and intestine.
Figure 6: Bursting force of Kollicoat DDS (SR/IR 7:3; 12 mg/cm²) after
needle pricking
45
40
35
30
25
20
15
10
5
0
bursting force [N]
force [N]
displacement [mm]
displacement [mm]
O 2 4 6 8 10 12 14 16 18 20 22 24
dissolution time [h]
7
6
5
4
3
2
1
0

No. 21, October 2008 | PAGE 9
ICH Q7 GMP Standard
Implemented for
1,2 Propylene Glycol Pharma
BASF SE has been producing
propylene glycols for more than
30 years and also has a long
experience in the manufacturing
of high purity propylene glycol.
The grade 1,2 Propylene Glycol
Pharma has for several years
been supplied to the pharmaceutical
industry as high-quality
excipient.
Propylene glycol is used in a
wide variety of pharmaceutical
formulations and is generally
regarded as safe. It is used as a
solvent, extractant and preservative
in a variety of parenteral and
non-parenteral formulations. It
has similar antiseptic properties
to ethanol.
And, last but not least, propylene
glycol is commonly used as a
plasticizer in aqueous film coating
formulations (e.g. it is particularly
suitable for a combination
with Kollicoat ® MAE 30 DP)
BASF SE now voluntarily fulfills
the requirements of a possible
basis for a GMP Directive “Specific
Conditions of the application
of the Principles and Guidelines
of Good Manufacturing
Practice for Certain Excipients”
which was published by the
EMEA in December 2006.
Even though it is unlikely that the
requirements of this draft Directive
will come into force, BASF
SE is committed to the high
GMP standard.
The introduction of GMP (ICH Q7)
will ensure the highest possible
quality of the excipient. 1,2
Propylene Glycol Pharma and
will – together with the (planned)
certification by the relevant
authority – provide added value
to our customers.
View on Production facility: 1,2 Propylene Glycol Pharma
The propylene glycols are manufactured
at the Glycol plant at
Ludwigshafen. 1,2 Propylene
Glycol Pharma is synthesized
using propylene oxide and water
as starting materials. The product
is backward integrated in the
Ludwigshafen Verbund site.
BASF has now implemented the
GMP quality standard ICH Q7 in
the production of 1,2 Propylene
Glycol Pharma. The equipment
was qualified and the process was
validated against this guideline.
Filling facility: 1,2 Propylene Glycol Pharma

Excipients & Actives for Pharma
Troubleshooting
Ideas and solutions
for R&D
and production
Film Coating: Scuffing
T. Cech 1 (thorsten.cech@basf.com), F. Wildschek 2 (florian.wildschek@basf.com)
1
BASF SE, European Pharma Application Lab, 67056 Ludwigshafen, Germany
2
BASF SE, New Business Development & Technical Service, 67056 Ludwigshafen, Germany
INTRODUCTION
Developing and manufacturing
of pharmaceutical dosage forms
can always lead to unexpected
problems. The more complex
a process gets, the higher the
risk of running into trouble.
In everyday work, you aim to
work as fast as possible. Timeconsuming
investigations of
what went wrong is often just
not possible.
This new section in ExAct
intends to fill this gap.
As we all know, experience is
the sum of the trials that went
wrong. So we want to show
what went wrong in the past,
either planned or unplanned.
We want to share our experience
in order to enable you recognize
non-optimal processes and find
ways to improve them.
In each upcoming ExAct, you
will find a column that deals with
a specific problem. You will also
find some background information
that explains the cause of
the problem and suggestions on
how to avoid the problem. We
hope this will support your daily
work.
Problem
You may have never heard of
scuffing and perhaps you don’t
even know the meaning of the
term. Nevertheless, we are certain
that you have encountered
this problem: grayish spots on
tablets coated white, or with
a light hue.
Scuffing effect on tablet surface

No. 21, October 2008 | PAGE 11
Table 2 – Excipients [2]
Titanium dioxide (E 171)
Specific gravity 3.8 – 4.1
Particle size
Ø 0.5 – 1 μm
Hardness (Mohs scale) 5 – 6
These spots are usually observed
after the final drying
phase of the coating process.
But initial indications can also
be found during the spraying
process, though these may be
less obvious and more difficult
pinpoint.
Reason
The typical formulation of a
brilliant white coating contains
large amounts of titanium dioxide.
This white pigment is wellknown
for its intensive color
properties and covering power.
The Mohs scale is of great help
in comparing the hardness of
different materials. In mineralogy,
hardness commonly refers to
a material’s ability to penetrate
softer materials. An object made
of a hard material will scratch an
object made of a softer material.
Scratch hardness is usually
measured on the Mohs scale
(Table 3). Pure diamond is the
hardest known natural mineral
substance and will scratch all
other materials.
Talcum (E 553 b)
Specific gravity 2.58 – 2.83
Particle size
Ø 10 – 20 μm
Hardness (Mohs scale) 1 – 1.5
Unfortunately, this widely used
excipient also has a hidden disadvantage
– its hardness.
Table 1 – Mohs Hardness
of Some Items
Scratch
Material
Hardness
2.5 Fingernail
2.5 – 3 Gold, Silver
3 Copper penny
4 – 4.5 Platinum
4–5 Iron
5.5 Knife blade
6 – 7 Glass
6.5 Iron pyrite
7+ Hardened steel file
Kaolin (E 559)
Specific gravity 2.61 – 2.68
Particle size
Ø 0.6 – 0.8 μm
Hardness (Mohs scale) 2.0 – 2.5

Excipients & Actives for Pharma
This scale of measurement can
be used to investigate to explain
the phenomenon of scuffing. A
look at the components involved
(tablets and coating equipment)
reveals some very interesting
details. Titanium dioxide is harder
than metal (Table 1 and 2).
According to the definition of the
Mohs hardness, titanium dioxide
causes scratches in the softer
material – the metal the coater
drum is made of. Hence, scuffing
is an abrasion effect.
For obvious reasons, it is not
feasible to erode a whole baffle
with titanium dioxide. However,
some metal oxides, some metal
atoms and impurities coming
from the coating batch would
invariably be etched on the coated
tablets – and this is what
causes the grayish discoloration
on the tablets’ surface.
Solution
If the aim is not to use whitecoated
tablets as a cleaning tool
– then one would have to use
additives to eliminate this scuffing
or scratching effect.
Table 3 – Hardness of Materials According to Mohs Scale [1]
Scratch Mineral Structure
hardness
This is where glidants are
extremely useful. Examples of
glidants include talcum or kaolin.
Both excipients are quite similar
in their properties. However,
Kaolin has some advantages
over talcum, a standard excipient
used in the pharmaceutical
industry. Kaolin has a smaller
particle size; which reduces the
sedimentation speed, leading
to less deposition of pigments
in the tubing. Furthermore, the
smaller particles result in film
with a smoother appearance.
As regards scuffing, the weaker
particles of talcum and kaolin
lubricate the movement of the
tablet on the metal surface. This
improves gliding on the coating
vessel, reduces abrasion, and
avoids scuffing.
The quantity of gliding agent
used depends on the batch
size, the type of coater used
(mechanical stress), the tablet
shape and the film-forming polymer.
There is no general recommendation.
A good starting point
would be to use at least 10%
glidant in the formulation.
1 Talcum Mg 3 Si 4 O 10 (OH) 2
2 Gypsum CaSO 4·2H 2 O
2 Kaolin Al 2 O 3 2SiO 2 2H 2 O
3 Calcite CaCO 3
4 Fluorite CaF 2
5 Apatite Ca 5 (PO 4 ) 3 (OH-,Cl-,F-)
5 – 6 Titanium dioxide TiO 2
6 Orthoclase KAlSi 3 O 8
7 Quartz SiO 2
8 Topaz Al 2 SiO 4 (OH-,F-) 2
REFERENCES
[1] Werkstoffkunde und Werkstoffprüfung,
14. Auflage, Wolfgang Weißbach
[2] Handbook of Pharmaceutical Excipients,
The Pharmaceutical Press
9 Corundum Al 2 O 3
10 Diamond C

No. 21, October 2008 | PAGE 13
News
All the latest from the
world of excipients
and active ingredients
USP
Pharmaceutical Ingredient
Verification Program
On July 31, 2008, BASF was
awarded its fourth USP certificate.
This means that the manufacturing
of PovidoneIodine
and the soluble Kollidon ® grades
at the BASF production sites
in Geismar, Louisiana/USA,
and Povidone, Copovidone
and Crospovidone production
plants in Ludwigshaven, have
passed the USP Verification
Program for pharmaceutical
ingredients. During the verification
process, USP conducted
very detailed on-site GMP-audits
of the production sites, reviewed
Kollicoat ® IR:
Draft Monograph for the European
Pharmacopoeia
For the first time, a draft monograph
for the excipient Kollicoat
IR by BASF has been published
in the European Pharmacopoeia.
This draft monograph appeared
under the title “Macrogol – poly -
vinyl alcohol – graft copolymer”
(#2523) in the 20/3 edition of
Pharmeuropa (The European Pharmacopoeia
Forum) of July 2008.
Kollicoat IR is a water-soluble
polymer that is used as a film for -
mer for the production of instantrelease
tablet coatings. This
enables active ingredients to be
released without delay shortly
after the tablets are taken. Using
Kollicoat IR it is possible to produce
high-quality, visually
appealing tablets of great
mechanical stability with out
the relevant manufacturing and
quality control/quality assurance
documentation, and performed
laboratory testing of the ingredients
in their own labs.
After examining the information
provided during the verification
process, USP finds that the
BASF Corporation’s and BASF
SE’s quality system provides
adequate assurance that the
reviewed ingredients meet the
applicable monograph requirements
set forth in the current
edition of the USP-NF.
requiring plasticizers. Moreover,
the polymer helps manufac turers
make the coating pro cess more
efficient and economical.
Solid oral dosage forms containing
Kollicoat IR have been ap -
proved in Germany since 2005
and in France, Great Britain,
Spain and Portugal since May
2007. In April 2008, the US Food
and Drug Administration (FDA)
licensed a drug with a Kollicoat
IR coating for the first time
(ANDA # 75-661). Kollicoat IR
has been registered in Japan
since August 2007.
Kollicoat IR is manufactured by
BASF in Germany according to
cGMP guidelines. The polymer is
marketed worldwide under the
Reliable and validated production
processes are indispensable
for high-quality products. The
USP certificates are written evidence
of BASF’s outstanding
standards.
brand name Kollicoat IR and is
also contained in the products
Kollicoat IR White (ready-to-use
preparation for white film coatings)
and Kollicoat Protect
(instant-release coatings for
moisture protection).
More detailed information is
available from
pharma-ingredients@basf.com
New certificates
(since July 31, 2008)
- USP Verification of
Povidone, Copovidone
and Crospovidone
production in
Ludwigshafen and
Geismar granted.
- PVP-I, Kollidon 30 and
Kollidon 17 production
at Geismar included.
New registrations
- US: Kollicoat IR White
ANDA for Kollicoat IR/
Ibuprofen 200 mg formu -
lation has been approved
by FDA in April 2008
- Russia: Vitamin A Acetat
Permanent Registration
Licence for Vitamin A
Acetate, 1.5 Mio oily
- China: Kollicoat IR
IDL for Kollicoat IR in place
New monographs
- Ph.Eur.: Kollicoat IR
Draft Monograph of
Kollicoat IR was published
in Pharmeuropa 20/3 for
discussion.
REGULATORY AFFAIRS

Excipients & Actives for Pharma
Workshops
Information
on upcoming
training events
“The Process from Powder to coated Tablet”
BASF SE invites you to a technical training event in
Loughborough, UK from October 22 to 23 and
Como, Italy from October 29 to 30
“The Effect of BASF’s Highly
Functional Excipients”
Free Webinar December 2
To register, go to
www.pharmaquality.com/BASF
Topics:
The effect of BASF’s highly
functional excipients for
improving solubility and
bioavailability of poorly
soluble drug
Speakers from BASF:
Dr. Anisul Quadir
Dr. Shaukat Ali
Speakers from BASF:
Dr. Michael Black;
Account Manager
Fokke Andreesen;
Head of Sales
Dr. Ole Christensen;
Quality Management /
Technical Marketing
In Loughborough only:
Dr. Verena Geiselhart;
Technical Marketing
Dr. Felicitas Guth;
Strategic Marketing
In Como only:
Maureen Mistry:
Technical Marketing
Inge Rademacher:
Strategic Marketing
Topics:
Presentation of BASF
Pharma Ingredients &
Services
BASF Pharma Ingredients
– Product Overview
Powder Properties
Ludiflash ®
Functional Coating
Polymers
Instant Release Coating
Polymers & Systems
The seminar will be held in
English.

No. 21, October 2008 | PAGE 15
New
Media
Information on
BASF products
Volker Bühler
Pharmaceutical
Technology
of BASF Excipients
Pharma Ingredients & Services.
Welcome to more opportunities.
New booklet: Pharmaceutical
Technology of BASF Excipients
In this 3rd edition of the booklet,
an overview is given on the functions
of our excipients in pharmaceutical
technology.
The 162-page publication deals
with the different dosage forms
(solid, semi-solid, and liquid) and
des cribes numerous applications
of the Kollidon ® , Kollicoat ® ,
Ludiflash ® , Ludipress ® , Lutrol ® E,
Lutrol F, Solutol ® , and Cre -
mophor ® Grades using typical
formulations as examples of
their functionality. The present
3rd edition of this booklet includes
additional recently launched
Kollidon (e.g. -CL-F,
-CL-SF, and VA 64 Fine) and
Kollicoat (-IR White, -Protect)
grades and puts more emphasis
on coating applications than previous
editions. Furthermore, the
important newer technology of
melt extrusion for the application
of Kollidon grades is described.
The new Ludipress and
Ludipress LCE Brochure
Our brochure explains how
Ludipress and Ludipress LCE
enable you to streamline your
manufacturing operations.
Ludipress means quicker, easier,
and more cost-effective tableting.
With Ludipress, you save precious
time on developing, analyzing
and blending. It is suitable for
low-dosage active ingredients.
Ludipress LCE is ideal for lozen -
ges, chewables, effervescent
tablets and modified-release
formulations.
The brochure can be ordered
with the attached reply card, or
directly via e-mail at
www.pharma-ingredients.
basf.com
Additional information on Ludipress
is available. Please
contact us, and we will introduce
Ludipress to you personally.
Coating with Kollicoat
A new poster is now available –
“Coating with Kollicoat”
(490 x 698 mm).
The poster provides you with
an overview on the current
Kollicoat portfolio – including
benefits, chemical name, composition,
and regulatory status
for each Kollicoat product.
Order your free poster from
your local BASF contact today.

Excipients & Actives for Pharma
Preview
In the next issue
of ExAct
Melt Extrusion for Pharmaceuticals
In the 1980s, BASF applied the
melt extrusion process, already
well known in the plastics industry,
to pharmaceuticals for the
first time.
As in the case of other breakthrough
innovations, numerous
obstacles had to be overcome
before commercialization of the
technology and resulting dosage
forms.
specific benefits like: enhanced
bioavailability of poorly soluble
drugs, reliable controlled-release
profiles, robust manufacturing
process, etc.
The criterion for a polymer to
be used in melt extrusion is
thermoplastic behavior, however,
the number of such polymers
approved for pharmaceutical
use is limited.
The article in the next issue of
ExAct will deal with the suitability
of polymers for melt extrusion,
and highlight requirements for
the process.
Based on the selection of a suitable
polymer, pharmaceutical
companies can improve dosage
form characteristics as well as
shorten the development period.
Melt extrusion technology is
BASF offers polymers with differ-
gaining increasing interest due to
ent structures and properties for
use in melt extrusion.
Calendar
Oct 22-Oct 23, 2008*
BASF Workshop on solid
dosage forms
Contact
Loughborough, UK
What opportunities can we
North America
open up for you?
BASF Corporation
Oct 29-Oct 30, 2008*
Simply contact your local BASF
Pharma Ingredients & Services
Important dates
BASF Workshop on solid
dosage forms
representative or one of the regional
offices listed below.
Javier Beeck
100 Campus Drive
Como, Italy
Alternatively, visit our website
Florham Park, NJ 07932
www.pharma-ingredients.basf.com
USA
Oct 28-Nov 30, 2008
Phone: +1 973 245-6381
Sep 9-Oct 2, 2008*
CPhI/PMEC India
Asia
javier.beeck@basf.com
CPHI Worldwide 2008
Mumbai, India
BASF East Asia Regional
Frankfurt, Germany
Headquarters Ltd.
South America
Dec 1-Dec 2, 2008
Pharma Ingredients & Services
BASF S.A.
Sep 9-Oct 2, 2008*
IPEC Conference
Thomas Pilgram
Pharma Ingredients & Services
Powtech 2008
Munich, Germany
45th Floor, Jardine House,
Vanessa Occhipinti
Nürnberg, Germany
No. 1 Connaught Place,
Avenida Faria Lima, 3600 – 9th floor
Dec 2-Dec 4, 2008
Central, Hong Kong
04538-132 São Paulo – SP
Oct 9-Oct 10, 2008
PharmaForce Europe
Phone: +852 27311-589
Brazil
Symposium on Pharmaceutical
Amsterdam, The Netherlands
thomas.pilgram@basf.com
Phone: +55 11 3043-3341
Melt Extrusion, from Concept to
vanessa.occhipinti@basf.com
Commercialization
Jan 27-Jan 30, 2009
Europe
Ludwigshafen and Heidelberg,
InformexUSA
BASF SE
Germany
San Francisco, USA
Pharma Ingredients & Services
Would you like to discuss a particular
Peter Hoffmann
challenge or product in more detail?
Oct 15-Oct 16, 2008*
Apr 21-Apr 23, 2009
G-EMP/EM – J 550
Or do you have any questions?
Compression workshop
CPHI, Japan
67056 Ludwigshafen
Simply call or e-mail us. We would be
IMA Kilian GmbH&Co.KG
IMA Kilian facility, Cologne,
Germany
Tokyo, Japan
* BASF participation
Germany
Phone: +49 621 60-76928
peter.wolfgang.hoffmann@basf.com
glad to help.
EMP 040102e-21