Suitability of Plasticized Polymers for Hot Melt Extrusion - Pharma ...

CONTENTS
Suitability of Plasticized Polymers
for Hot Melt Extrusion PAGES 2–6
Ludiflash ® – Preparation and Characterization
of Orally Disintegrating
Mini-Tablets for Pediatric Use PAGES 7–10
Ludiflash as Excipient for
Pediatric Use PAGE 11
Color Matching for Instant-
Release Coated Tablets PAGES 12 –14
Trouble-Shooting in Film Coating:
Deposition and Sedimentation PAGES 15 –16
PVP (polyvinylpyrrolidone):
An All-Round Talent with Tradition PAGE 17
REGULATORY AFFAIRS PAGES 18 – 19
NEW MARKETING ASSETS PAGE 19
CALENDAR PAGE 20
PREVIEW PAGE 20
CONTACT PAGE 20
IN FOCUS
Today, in pediatrics, a
large number of drugs
are unlicensed or prescribed
off-label, i.e.
despite a lack of information
on how to
prescribe safely. Thus,
the use of innovative
medication with children
is often impossible.
Moreover, in
general, off-label use is associated with more adverse
reactions to drugs used for children. Not only
that, the reactions may be more severe or different
from what is known from use in adults.
The EU regulations on the use of pediatric drugs
represent a first step towards improved child
health. BASF goes along with this approach by
offering Ludiflash, a directly compressible excipient
for orodispersibles. It can be applied successfully
to the production of mini-tablets for
pediatric use, enabling individual dosages to be
calculated and making for easy administration to
young patients. A further aid is our special safety
report for Ludiflash which helps pharmaceutical
companies overcome regulatory hurdles in developing
medication for children.
Excipients & Actives for Pharma
Suitability of Plasticized Polymers
for Hot Melt Extrusion
Dear Reader: How can we overcome the hurdles involved
in medicating children?
No. 24, 2010
Designed to investigate the influence of several solubilizers and plasticizers on the extrusion process
and extrudate characteristics, the present study shows, among other conclusions, that the combination
of certain materials can significantly change the glass transition temperature and the melt viscosity
of the extrudate polymers. READ MORE ON PAGES 2 –6
Innovative and promising technologies such as
hot melt extrusion can be supported by the combination
of various polymers with selected plasticizers
and active ingredients. We provide further
insights in this edition: how are formulation properties
changed by certain additives, and what can
be used in order to achieve particular characteristics,
either during processing or in the final formulation?
Find out how we can make drug developers more
successful in designing optimized and robust formulations,
hence speeding up the development
process. Our solubilization experts around the
world will be happy to discuss your solubilization
challenges with you!
Yours sincerely,
Dejan Djuric
R&D Pharma Ingredients

PUBLISHER:
BASF SE
Pharma Ingredients & Services
www.pharma-ingredients.basf.com
EDITORIAL STAFF:
Alexandra Brand
Andres-Christian Orthofer
Karl Kolter
Vanessa Occhipinti
AUTHORS:
Angelika Maschke
Claudia Easterbrook
Dorothee-Christine Kriha
Christian Becker
Florian Wildschek
Friederike Osswald
Ines Stoltenberg
Jörg Breitkreutz
Karl Kolter
Matthias Karl
Michael Gerrit Herting
Philipp Hebestreit
Ralf Widmaier
Sebastian Hoefer
Thorsten Cech
Thorsten Schmeller
CONCEPT/LAYOUT:
Château Louis Strategische Markenführung
und Kommunikation GmbH
PRINT:
Page 2
IMPRINT
johnen-druck GmbH & Co. KG
Trademarks are owned by BASF SE
Excipients & Actives for Pharma
IN FOCUS
Suitability of Plasticized Polymers
for Hot Melt Extrusion
M. Karl, K. Kolter
> INTRODUCTION | Melt extrusion is a highly
suitable process for formulating sparingly soluble
drugs and for improving bioavailability [1]. In
ExAct No. 22, we described the principle and the
basic requirements of the process [2]. The choice
of an appropriate polymer is crucial for the formulation
and for the extrusion process. Polymers
for hot-melt extrusion (HME) should have the
thermoplastic behavior to enable melt extrusion
to take place and they have to be stable at the
extrusion temperature. Other relevant characteristics
are: a suitable glass transition temperature
(Tg) of 50 to 180°C, low hygroscopicity and no
toxicity, since large amounts of polymer are used
[3]. The extrudability of a polymer is mainly determined
by the Tg and the melt viscosity [4].
Polymers of high molecular weight exhibit a high
melt viscosity and are difficult to extrude. Moreover,
a high Tg requires a high processing temperature,
which can degrade sensitive actives [5].
As a general rule, an extrusion process should be
run at a temperature 20-40°C above the Tg. Polymer
properties for hot-melt extrusion can be adjusted
by the use of plasticizers since these
materials reduce the Tg and melt viscosity and
also facilitate the extrusion process [6, 7]. Lowering
the extrusion temperature reduces degradation
and/or discoloration of the polymer and
increases drug stability in the pharmaceutical
formulation. Therefore, the study described here
was designed to investigate the influence of several
plasticizers/solubilizers on the Tg, the melt
viscosity, the temperature range for extrusion and
the extrudate characteristics of various polymers.
POLYMERS AND PLASTICIZERS | The polymers
studied were: Kollidon ® VA 64, Kollidon 12
PF, Kollidon 17 PF, Kollidon 30, Kollidon 90 F,
Kollidon SR, Soluplus ® , Kollicoat ® MAE 100P,
Kollicoat IR and Lutrol ® F 127 (BASF SE, Germany).
The plasticizers studied were: Lutrol F 68,
Cremophor ® RH 40 and Pluriol ® E 1500 Powder K
(PEG 1500) (BASF SE, Germany).
No. 24, 2010
RESULTS AND DISCUSSION | All polymers
were characterized by their glass transition temperature
(Tg), melt viscosity and degradation
temperature (T(degradation)) as indicated by onset
of mass loss in thermogravimetric measurements
(TGA).
A large range between
the glass transition temperature
and degradation
temperature of the polymers
is highly beneficial
because it offers more
freedom for the development
of the extrusion
process.
Taking these characteristics into consideration,
Soluplus, Kollidon VA 64 and Kollidon 12 PF
demonstrated excellent suitability for extrusion.
Kollidon 17 PF, Kollidon SR and Kollicoat IR were
difficult to extrude because of the higher Tg or
Tm (melting point), melt viscosities and the
smaller difference of T(degradation) to Tg or Tm
(Figure 1). Povidones of higher molecular weight
(Kollidon 30 and Kollidon 90 F) and Kollicoat MAE
100P exhibited poorer values in this respect and
were not processable by HME as pure polymers.
A large range between Tg and T(degradation) is
highly beneficial because it offers more freedom
for the development of the extrusion process and
also serves as a prerequisite for a reliable and
reproducible formulation.

Temperature [°C]
Excipients & Actives for Pharma
FIGURE 1 Comparison of the Tg or Tm (by DSC) with the temperature of degradation (by TGA) of pure polymers
Tg [°C]
300
250
200
150
100
50
0
180
160
140
120
100
80
60
40
20
0
101
Kollidon VA 64
230
101 103
83
Kollidon
VA 64
90
54
225
Kollidon 12 PF
138
Kollidon 17 PF
175
Pure polymer
Lutrol F 68
Cremophor RH 40
PEG 1500
175
149
70
47 50
42
Soluplus
90 92
71 67
Kollidon 12
PF
FIGURE 2 Tg of pure polymers in comparison with polymer-plasticizer combinations (extrudates, 9:1, w/w-%)
Kollidon 30
156
Kollidon 90 F
200
152
Kollidon SR
210
70
250
Soluplus
114
150
Kollicoat MAE
100P
Tg (or *Tm)
T degradation
208 200
Kollicoat IR*
138137
55
180
Lutrol F127*
109
102
Kollidon 17
PF
No. 24, 2010
Subsequently, the influence of plasticizers such
as Lutrol F 68, Cremophor RH 40 and PEG 1500
on the above-mentioned parameters was investigated
(Figures 2 and 3). In systems comprising
PEG 1500 and Cremophor RH 40, the results
showed a pronounced tendency to decrease the
Tg of the polymers. In polymer combinations with
Lutrol F 68, the Tg of the vinylpyrrolidone polymers
was practically unaffected by this compound
[8].
The impact of plasticizers on the melt viscosity of
Kollidon VA 64 is illustrated in Figure 4. A considerable
reduction of the melt viscosity was
achieved by adding plasticizer, increasing in the
following order: Cremophor RH 40 < PEG 1500 <
Lutrol F 68. Since Lutrol F 68 reduced the melt
viscosity substantially but did not significantly affect
Tg, it can be concluded that it is probably not
completely miscible with the polymers tested.
The plasticizer-polymer combinations characterized
by lowered Tg and melt viscosity extended
the temperature range for extrusion since this
could be performed at lower temperatures [9].
Melt extrusion studies to determine the lower end
of the temperature range revealed the strongest
effect for PEG 1500 (Figure 5). This can be attributed
to the strong decline of Tg as well as to the
significant reduction of melt viscosity.
Page 3

Tg [°C]
FIGURE 3 Tg of pure polymers in comparison with polymer-plasticizer combinations (extrudate and film (*), 9:1, w/w-%)
Split bars represent the presence of another Tg
Viscosity [Pa*s]
FIGURE 4 Melt viscosity of Kollidon VA 64 in comparison with Kollidon VA 64 / plasticizer combinations (9:1, w/w-%)
Page 4
180
160
140
120
100
80
60
40
20
0
10000
1000
100
Excipients & Actives for Pharma
149
10
129
101
118
156
146
133
128
152 155
Kollidon 30 (*) Kollidon 90 F (*) Kollidon SR
Kollidon VA 64
Kollidon VA 64 / Cremophor RH 40 (9:1)
Kollidon VA 64 / Lutrol F 68 (9:1)
Kollidon VA 64 / PEG 1500 (9:1)
140 150 160 170 180 190 200 210
Temperature [°C]
39
18
118
32
25
Pure polymer
Lutrol F 68
Cremophor RH 40
PEG 1500
Optimum
melt
viscosity
range for
HME
No. 24, 2010
The extrudates of Kollidon ® VA 64 obtained using
PEG 1500 as the plasticizer were transparent,
whereas extrudates with Lutrol ® F 68 and Cremophor
® RH 40 were opaque. For both opaque
systems, the signals produced by Lutrol F 68 and
Cremophor RH 40 respectively were monitored by
differential scanning calorimetry (DSC). For the
transparent extrudate with PEG 1500, no PEG
1500 signal was observed. In accordance with
these findings, in combination with Lutrol F 68, the
Tg of Kollidon VA 64 at approx. 101°C could still
be determined and in the cases of Cremophor
RH 40 and PEG 1500, the Tg was shifted to lower
temperatures [10].
Based on these DSC results (Figures 6 to 8) and
on visual inspection, it can be concluded that PEG
1500, in contrast to the others, forms a singlephase
mixture when melt-extruded with Kollidon
VA 64. In other words, it is completely miscible.

CONCLUSION
REFERENCES
Excipients & Actives for Pharma
� The type of plasticizer used has a major impact
on the relevant characteristics of the
extrusion process and the extrudates. Plasticizers
influence the Tg, melt viscosity, temperature
range for extrusion and extrudate
properties.
� The addition of PEG 1500 and Cremophor
RH 40 reduces the Tg of the polymer considerably.
� All plasticizers lowered the melt viscosity
when added to Kollidon VA 64.
� All plasticizers extended the lower end of
the temperature range for extrusion, but this
was most pronounced with PEG 1500.
� The presence of plasticizer signals in DSC
runs correlates with the appearance of extrudates
and indicates miscibility or non-miscibility
on a molecular basis. |
[1] C. Leuner and J. Dressman, Improving drug
solubility for oral delivery using solid dispersions,
European Journal of Pharmaceutics
and Biopharmaceutics, 50, 47-60 (2000)
[2] K. Kolter and A. Maschke, Melt Extrusion for
Pharmaceuticals, ExAct, No. 22 (2-5) (2009)
[3] I. Ghebre-Sellassie, C. Martin, Pharmaceutical
Extrusion Technology, Drugs and the
Pharmaceutical Sciences, Volume 133 (2007)
[4] R. J. Chokshi, H. K. Sandhu, R. M. Iyer, N.
H.Shaw, A. W. Malick and H. Zia, Characterization
of physico-mechanical properties of
indomethacin and polymers to assess their
suitability for hot melt extrusion processes
as a means to manufacture solid dispersion/solution,
Journal of Pharmaceutical
Science, 94, (11, 2463-2474 (2005)
[5] S. Thumma, M. A. ElSohly, S. Q. Zhang,
Temperature [°C]
FIGURE 5 Temperature range for extrusion of the pure polymers in comparison with polymer / PEG 1500 combination (9:1, w/w-%)
FIGURE 6 DSC plot of Kollidon VA 64, Lutrol F 68 and a combination of Kollidon VA 64 / Lutrol F 68 (extrudate, 9:1, w/w-%)
No. 24, 2010
50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240
Heat flow [W/g]
8
6
4
2
0
Kollidon VA 64
Lutrol F 68
Kollidon VA 64 / Lutrol F 68
Kollidon 12 PF
Kollidon VA 64
Kollidon SR
Soluplus ®
Kollicoat ® IR
Kollidon 17 PF
Extrudate:
Kollidon VA 64 / Lutrol F 68
Pure polymer
+ 10% PEG 1500
-2
-100 -50 0 50 100 150 200
Temperature [°C]
Page 5

Heat flow [W/g]
Heat flow [W/g]
Page 6
3
2
1
0
Kollidon ® VA 64
Cremophor ® RH 40
Kollidon VA 64 /
Cremophor RH 40
-1
-100 -50 0 50 100 150 200
10
8
6
4
2
0
-2
Excipients & Actives for Pharma
Kollidon VA 64
PEG 1500
Kollidon VA 64 / PEG 1500
Temperature [°C]
Extrudate:
Kollidon VA 64 / Cremophor RH 40
FIGURE 7 DSC plot of Kollidon VA 64, Cremophor RH 40 and a combination of Kollidon VA 64 / Cremophor RH 40
(extrudate, 9:1, w/w-%)
Extrudate:
Kollidon VA 64 / PEG 1500
-100 -50 0 50 100 150 200
Temperature [°C]
FIGURE 8 DSC plot of Kollidon VA 64, PEG 1500 and a combination of Kollidon VA 64 / PEG 1500 (extrudate, 9:1, w/w-%)
No. 24, 2010
W. Gul, M. A. Repka, European Journal of
Pharmaceutics and Biopharmaceutics, 70
(2), 605-614 (Oct. 2005)
[6] A. Ghebremeskel, C. Vemavarapu and
[7]
M. Lodaya, Use of surfactants as plasticizers
in preparing solid dispersions of
poorly soluble API, International Journal of
Pharmaceutics, 328, 119-129 (2007)
M. A. Repka, S. Majumdar, S. K. Battu, R.
Srirangam and S. B. Upadhye, Applications
of hot-melt extrusion for drug delivery, Expert
Opinion on Drug Delivery, 5 (12):
1357-1376 (2008)
[8] M. Baiardo, G. Frisoni, M. Scandola,
[9]
M. Rimelen, D. Lips, K. Ruffieux, E. Wintermantel,
Thermal and mechanical properties
of plasticized poly (L-lactic acid), Journal of
Applied Polymer Science, 90 (7), 1731-1738
(Sep. 2003)
C. B. Wu, J. W. McGinity, Influence of
methylparaben as a solid-state plasticizer on
the physicochemical properties of Eudragit ®
RS PO hot-melt extrudates, European Journal
of Pharmaceutics and Biopharmaceutics,
56 (1), 95-100 (Jul. 2003)
[10] K. Okamoto (Okamoto, Kenzo); T. Ichikawa
(Ichikawa, Tomokazu); T. Yokohara (Yokohara,
Tadashi); M. Yamaguchi (Yamaguchi,
Masayuki); Miscibility, mechanical and thermal
properties of poly (lactic acid) / polyester-diol
blends, European Polymer Journal,
45 (8), 2304-2312 (Aug. 2009)

CHILDREN´S MEDICATION
Excipients & Actives for Pharma
Ludiflash ® – Preparation and Characterization of Orally
Disintegrating Mini-Tablets for Pediatric Use
I. Stoltenberg, J. Breitkreutz (Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany)
> orally-disintegrating tablets made with Ludiflash
INTRODUCTION | Young children often have
no access to suitable medicines. To deal with
this, both the US and the EU authorities implemented
new pediatric regulations requiring
increased efforts in the development of pediatric
formulations. The desired properties of pediatric
dosage forms are easy administration, good or
acceptable taste, the possibility for dose titration
and safe excipients.
Orally-disintegrating mini-tablets (ODMTs) are
defined as small tablets with a diameter of 3 mm
or less and a disintegration time of less than 30
seconds. These are particularly suitable for
younger children (> 1 month) [1]. Easy administration
without the need for additional water is a
major advantage. Due to the fast disintegration
of the tablets, it is difficult for children to spit them
out. Furthermore, they may provide accurate individualized
dosing, for example according to the
body weight or body surface area of the children.
In addition, two or more mini-tablet formulations
can be combined to generate fixed dose combinations
of different active pharmaceutical ingredients
(APIs). The combination of mini-tablets
based on various release principles is a further
possibility. ODMTs provide the convenience of a
tablet formulation but also the ease of swallowing
allowed by liquid formulation.
They can be manufactured using conventional
tableting facilities but necessitate excipients
which fulfill the requirements for direct compression
of tablets. The excipients should have good
flow characteristics and good compactibility,
especially with regard to the small-dimensioned
mini-tableting tool. Ludiflash is a new coprocessed
ready-to-use excipient for fast-disintegrating oral
dosage forms. It is made from D-mannitol, crospovidone
(Kollidon CL-SF, BASF SE), polyvinyl
acetate (Kollicoat ® SR 30D, BASF SE) and povidone
(Kollidon 30, BASF SE). All components
comply with leading pharmacopoeia monographs.
Concerning the high amount of sweettasting
but non-cariogenic D-mannitol (90%),
should prove to be very palatable for children.
D-mannitol is deemed to be a safe excipient for
children [2].
PURPOSE | The purpose of this study was to
investigate the feasibility of Ludiflash as an excipient
for the direct compression of ODMTs for
pediatric use.
METHODS AND MATERIALS | Materials
Ludiflash (BASF SE), sodium stearyl fumarate
(Pruv ® , JRS Pharma), magnesium stearate (Bärlocher
GmbH).
Experimental design An eleven-run full factorial
design (including three replicates of the
center point) was used to evaluate three variables
(type of lubricant, lubricant concentration and
compression force) with respect to the ODMTs
properties, crushing strength and simulated wetting
test time.
Preparation of mini-tablets All ingredients
were blended in a Turbula blender (Bachofen SE)
for 10 minutes and directly compressed into
biconvex mini-tablets of 2 mm diameter using a
rotary tablet press (Pressima MX-EU-B/D, IMA
Kilian GmbH & Co KG) with one 19-tip minitableting
tool (Ritter Pharmatechnik GmbH).
Simulated Wetting Test (SWT) The wetting
time of the ODMTs was evaluated according to a
method described by Park et al [3]. One Whatman
filter paper disk (5 mm in diameter) was
placed in each well of a 96-well plate. 20 µl of
0.1% (w/w) Brilliant Blue 85 E 133 solution (BASF
SE) was added to each well. One ODMT was
carefully placed on the surface of the wet paper
disk in each well using a pair of forceps. The level
of the dye solution did not cover the tablet. The
time required for the blue dye solution to wet the
tablet completely was measured as the simulated
wetting test time.
No. 24, 2010
Crushing strength The crushing strength was
measured using a texture analyzer (TA-XT2i,
Stable Micro Systems). [4]
The desired properties of
pediatric dosage forms
are easy administration,
good or acceptable taste,
the possibility for dose
titration and safe excipients.
Flowability The flowing properties of the powder
blends were determined using a ring shear
tester RST-01.pc (Dr. Dietmar Schulze, Schuettgutmesstechnik).
The ratio ffc of consolidation
stress σ1 to unconfined yield strength σc was
used to characterize flowability numerically (Table
1). The pre-shear normal stress was constant at
about 5000 Pa.
Numerical characterization of flowability
ffc

FIGURE 1 ODMTs made from Ludiflash and 3%
sodium stearyl fumarate (2 mm diameter)
N1
N2
N3
N4
N5
N6
N7
N8
N9
N10
N11
TABLE 2 Results of the experimental design
Page 8
Excipients & Actives for Pharma
Type of lubricant
Sodium stearyl fumarate
Magnesium stearate
Sodium stearyl fumarate
Magnesium stearate
Sodium stearyl fumarate
Magnesium stearate
Sodium stearyl fumarate
Magnesium stearate
Sodium stearyl fumarate
Sodium stearyl fumarate
Sodium stearyl fumarate
Lubricant
concentration
[%]
2
2
5
5
2
2
5
5
3.5
3.5
3.5
FIGURE 2 Simulated wetting test of an ODMTs with 5%
magnesium stearate, produced with 3 kN
Compression
force
[kN]
3
3
3
3
8
8
8
8
5.5
5.5
5.5
0 s 4 s 6 s
8 s 10 s
SWT time
(n=10)
[s]
1.55
3.25
2.17
7.78
3.42
6.68
6.17
21.05
2.96
2.94
2.89
Crushing
strength
(n=30)
[N]
4.80
4.11
4.49
3.95
10.78
10.76
11.99
9.31
8.31
8.80
8.04
No. 24, 2010
RESULTS AND DISCUSSION | Preliminary
experiments The flowability of blends of Ludiflash
® and used lubricant were tested using the
ring shear cell. All samples showed an ffc value
>10, which implies excellent flow properties. This
allows uniform filling of the small dies during the
tableting operation. Since mini-tableting tools are
very fragile, good compactibility properties are
required. Preliminary experiments indicated that
only low forces (

Excipients & Actives for Pharma
CONCLUSION | Orally disintegrating mini-tablets
are supposed to be very useful formulations for
the treatment of young children and may be considered
as a new technology platform in pediatrics.
The criteria of the World Health Organization
(WHO), such as the use of standard excipients
and conventional techniques, are fully met [6].
Due to its excellent properties for the direct compression
of mini-tablets (good flowing behavior,
good compactibility), Ludiflash is suitable for
manufacturing this new dosage form. The lubricant
sodium stearyl fumarate outperforms magnesium
stearate in crushing strength and SWT
time. A compression force between 5 and 8 kN
(approx. 80-130 MPa) should be applied to
achieve ODMTs with sufficient crushing strength
(above 8 N). Excellent SWT times of less than 4
seconds were obtained using 2-3.5% sodium
stearyl fumarate. |
Crushing strength [N]
14
12
10
8
6
4
2
0
0 2 4 6 8 10
Compression force [kN]
FIGURE 3 Crushing strength and compression force profile of Ludiflash-ODMTs with 3% sodium stearyl fumarate,
n=30, mean ± SD, R²=0.9982
Simulated wetting test time [s]
0.25
0.20
0.15
0.10
0.05
0.00
-0.05
-0.10
-0.15
-0.20
-0.25
Sostefu
Mgste
LC
FIGURE 4 Coefficient plot for the simulated wetting test time; R²adj. = 1.000, Q² = 0.999; sodium stearyl fumarate (Sostefu),
magnesium stearate (Mgste), lubricant concentration (LC), compression force (CF)
CF
Sostefu*LC
Mgste*LC
Sostefu*CF
Mgste*CF
LC*SF
No. 24, 2010
Page 9

REFERENCES
Page 10
Excipients & Actives for Pharma
[1] Krause J, Breitkreutz J. Improving drug delivery
in pediatric medicine. Pharm Med. 2008;
22:41-50
[2] Breitkreutz J. Kindgerechte Arzneizubereitungen
zur peroralen Anwendung, Habilitationsschrift,
2004
[3] Park J. H., Holman K. M., Bish G. A., Krieger
D.G., Ramlose D. S., Herman C. J., Wu S. H..
An alternative to the USP disintegration test
for orally disintegrating tablets. Pharm. Tech.
2008; 32:54-58
[4] Mittwollen J-P. Verdichtungsverhalten, Festigkeit
und Struktur von planen Minitabletten,
Dissertation, 2002
[5] Jenike AW. Storage and flow of solids. Bull.
No. 123; Engng. Exp. Station, Univ. Utah,
Salt Lake City; 1964
[6] WHO, Report of the informal expert meeting
on dosage forms of medicines for children.
http://www.who.int/selection_medicines/committees/expert/17/application/paediatric/Dosage_form_reportDEC2008.pdf.
Accessed December 15, 2009
Crushing strength [N]
0.25
0.20
0.15
0.10
0.05
0.00
-0.05
-0.10
Sostefu
Mgste
LC
CF
Sostefu*LC
Mgste*LC
Sostefu*CF
Mgste*CF
FIGURE 5 Coefficient plot for the crushing strength; R²adj. = 0.932, Q² = 0.603, sodium stearyl fumarate (Sostefu), magnesium
stearate (Mgste), lubricant concentration (LC), compression force (CF)
LC*SF
No. 24, 2010

CHILDREN´S MEDICATION
Excipients & Actives for Pharma
Ludiflash ® as Excipient for Pediatric Use
P. Hebestreit, F. Osswald, R. Widmaier, M. G. Herting
Ludiflash ® is a formulation for fast-disintegrating
solid oral dosage forms. The formulation of
co-processed ingredients consists of three compendial
excipients: D-mannitol, crospovidone
(Kollidon ® CL-SF) and a polymer dispersion
based on polyvinyl acetate (Kollicoat ® >
SR 30 D).
It is designed to disintegrate on the tongue within
a few seconds, giving a pleasant mouthfeel. Ludiflash
is suitable for direct compression manufacturing
by simply blending the excipient with the
active ingredient and a lubricant; it is thus a very
cost-efficient production method.
Many drugs are currently not available in formulations
suitable for administration to pediatric patients.
Ludiflash, formulated as orally disintegrating minitablets
(ODMTs), is especially suitable for pediatric
use and may be considered an innovative technology
platform for pediatric formulations.
With Ludiflash, such ODMTs can be obtained in
sizes as low as 1 mm diameter. Disintegration of
such small ODMTs can be complete within a second
or less than 10 seconds, depending on size
and formulation.
Considering the recent
development and current
regulations on pediatrics,
BASF decided to
support its customers by
creating a special safety
report for Ludiflash.
1. Sufficient bioavailability (despite children´s particularities)
2.
3.
4.
5.
6.
7.
8.
Criteria for drug dosage forms appropriate for children [1]
Non-toxic excipients regarding age group and administration
Palatable or acceptable organoleptic properties
Acceptable dose uniformity
Easy and safe administration
Socio-cultural acceptability (no stigmatization)
Precise and clear product information
Convenient for parents
Considering the recent development and current
regulations on pediatrics (Regulation (EC) No
1901/2006 of the European Parliament and of the
Council of 12 December 2006 on medicinal products
for pediatric use and amending Regulation
(EEC) No 1768/92, Directive 2001/20/EC, Directive
2001/83/EC and Regulation (EC) No 726/2004
and/or concept paper on the development of a
quality guideline on pharmaceutical development
and medicines for pediatric use,
EMEA/138931/2008), BASF decided to support
its customers by creating a special safety report
for Ludiflash.
Ludiflash comprises 84.0-92.0% mannitol, 4.0-
6.0% crospovidone, 3.5-6.0% polyvinyl acetate
and 0.25-0.60% povidone (component of Kollicoat
SR 30 D). A summary of the relevant safety
data in the scientific literature and BASF’s own
No. 24, 2010
safety data have been compiled. This safety data
sheet is available upon request and also on the
company’s webpage http://www.pharma-ingredients.basf.com/ludiflash/default.aspx.
Extensive
safety and toxicological reports performed by
BASF are available under a secrecy agreement.
In summary, the safety report reveals that there are
no hindrances stemming from toxicological studies
or clinical experiences with Ludiflash to prevent
use of the excipient in pediatric patients. |
REFERENCES
[1] J. Breitkreutz, J. Boos, Exp. Opin. Drug Deliv.
4: 37-45 (2007)
Page 11

FILM COATING
INTRODUCTION | Color plays an important
role in the development of solid oral dosage
forms. Regarding the safety of tablets, fast identification,
not only by shape and size, but color, is
of great advantage. Although patients prefer
small white tablets, colored tablets increase both
drug safety and patient compliance [1]. Often,
tablets containing the same drug but varying in
strength are of a different color to help patients
distinguish between them. This is particularly the
case for elderly patients undergoing multi-drug
treatment as the differentiation of tablets by color
is enhanced. Furthermore, the psychological
effect of color can increase drug efficacy [2].
From a marketing point of view, the recognition
value of a color can be used to create a special
brand. The new product range of Kollicoat ® >
IR
Coating Systems – consisting of 7 ICH-approved
basic colors – for example has been designed to
facilitate the convenient and short production of
instant release coated tablets of a certain color
[3]. This is done by combining the different basic
colors at the production plant. The coating systems
are composed of the film-forming polymer
Kollicoat IR, a PEG-PVA grafted copolymer [4],
pigments and further additives. Special software
has been developed that makes the color prediction
of combinations of the different basic colors
possible. The goal of this study was to investigate
the potential to produce tablets of a certain
color using the Kollicoat IR Coating Systems in
combination with a color matching function
based on an algorithm of the colorimetric data of
the colors. Evaluation was performed by color
matching products already on the market.
MATERIALS | Instant release colored coating
systems Kollicoat IR White II, Kollicoat IR Yellow,
Kollicoat IR Red, Kollicoat IR Carmine, Kollicoat
IR Sunset Yellow and Kollicoat IR Brilliant Blue
(BASF SE, Germany) were used as coating
materials. The coloring pigments were titanium
dioxide, iron oxide yellow/red, and the aluminum
Page 12
Excipients & Actives for Pharma
Color Matching for Instant Release Coated Tablets
A. Maschke, T. Schmeller, K. Kolter
FIGURE 1 Schematic color matching procedure
Color or tablet selection
Color measurement
Recipe calculation with algorithm
Film coating of tablets
Color measurement of tablets
Determination of color deviation Delta E
lakes Carmine, Sunset Yellow and Brilliant Blue,
respectively. The core formulation of the tablets
was 99.5% Ludipress ® LCE (BASF SE, Germany)
and 0.5% magnesium stearate (Baerlocher
GmbH, Germany).
METHODS | The first step in the color matching
procedure was to determine the color of the original
tablets by colorimetric evaluation (Datacolor
400, Datacolor, USA). Based on the L*a*b* values
obtained, recipes for color matching were calculated
using the previously-mentioned algorithm.
The color of the tablets coated with the suggested
formulations was determined and the
color deviation then evaluated. Color adjustment
was carried out by adapting the recipes (see
Figure 1).
Color adjustment
No. 24, 2010
The experimental setup for colorimetric evaluation
was: aperture USAV, light source d65 and
observer angle 10°. The colorimetric values were
recorded as L*a*b* values of the CIELAB color
space and color deviation was calculated by determining
the Delta E value as displayed in Equation
1.
∆ E = (L*1- L*2) 2 + (a*1- a*2) 2 + (b*1- b*2) 2 (1)
EQUATION 1 Equation to calculate Delta E value

-a*
FIGURE 2 2D visualization of L*a*b* values of 100 different tablet colors coated with mixtures of Kollicoat IR Coating Systems
Tablet Color L* a* b*
1
2
3
4
5
6
7
8
9
10
60
50
40
30
20
10
0
-10
-20
-30
Excipients & Actives for Pharma
yellow
yellow
orange
yellow
pink
red
red
green
blue
blue
TABLE 1 Colorimetric data of marketed products
+b*
-40
-40 -30 -20 -10 0 10 20 30 40 50 60
-b*
81.0
74.7
72.6
92.4
88.7
65.6
88.6
74.9
75.4
69.4
14.1
12.4
24.9
3.5
11.4
27.0
8.4
-7.7
-8.1
-7.3
+a*
100
80
60
40
20
0
L*
28.5
40.7
21.4
23.3
8.9
19.9
10.8
7.1
-18.7
-21.7
No. 24, 2010
FILM COATING | Tablets were coated using a
fluid bed coater with a central rotating spraying
nozzle (Ventilus IEV1, Innojet Herbert Huettlin),
Germany). Aqueous film coating suspensions
with 20% solids content were prepared by redispersion
of mixtures of the Kollicoat IR Coating
Systems in water. For the film coating trials, a
batch size of 150 g was used and the coating
level was set to 3.2% weight gain (4.9 mg/cm 2 ).
RESULTS AND DISCUSSION | By simply combining
the different colored Kollicoat IR Coating
Systems, a large color space became accessible,
as shown for 100 colors in Figure 2.
For testing color matching, 10 commercially
available tablets of different color shades were
selected. The colorimetric data were used (see
Table 1) to calculate the recipes for color matching
(see Table 2). Those recipes with the smallest
variation of basic colors were selected. In evaluating
the L*a*b* values of the matched tablets,
color deviations below a Delta E of 2.5 were observed
(see Figure 3). This color deviation is usually
not detectable by the untrained eye, when
applied to the relatively small dimensions of a
tablet. Furthermore, even within one batch of
coated tablets, color differences of up to a Delta
E of 3 were detected (data not shown).
The color matching procedure is an iterative
process; therefore, generating a matching recipe
within the first cycle is an excellent result. To show
the effect of adjusting the recipe, a color matching
process in two steps is shown in Table 3.
Evaluation of the L*a*b* values showed that lowering
the red and yellow pigment content reduced
the Delta E. Exchanging Kollicoat IR Red by Kollicoat
IR Sunset Yellow in the recipe further reduced
the Delta E from 2.0 to 1.3.
Page 13

Kollicoat
Tablet White ||
® IR
1
2
3
4
5
6
7
8
9
10 92.5
TABLE 2 Recipes for color matching
Delta E
FIGURE 3 Delta E values of color-matched tablets
Page 14
[%]
85.0
50.0
87.2
95.7
97.3
75.0
98.5
88.3
98.4
Excipients & Actives for Pharma
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
Yellow
[%]
14.0
49.6
4.6
4.3
1.7
11.5
1.0
9.5
Red
[%]
1.0
0.4
5.5
13.5
0.5
Sunset
Yellow
[%]
0.5
0.2
Carmine
[%]
0.8
1.3
0.9
4.5
Brilliant
Blue
[%]
1.0
0.7
3.0
a) L* a* b*
Tablet
Recipe 1
Recipe 2
Recipe 3
b) Kollicoat IR
White ||
Yellow
Red
Sunset
Yellow
89.9
88.1
89.7
90.4
8.2
9.2
TABLE 3 Refinement of color matching
18.4
19.0
6.9 16.9
8.8
19.5
DE
0.0
2.2
2.0
1.3
Recipe 1 Recipe 2 Recipe 3
95.6
1 2 3 4 5 6 7 8 9 10
4
0.4
96.7
96.7
3 2.9
0.3
0
0 0 0.4
CONCLUSION | The Kollicoat IR Coating Systems
product line enables the color matching of
tablets. In combination with a BASF-proprietary
algorithm, a fast and economical color matching
procedure is possible. Due to the large accessible
color space, a desired color can be prepared by
the combination of different Kollicoat IR Coating
Systems. |
REFERENCES
No. 24, 2010
The color matching procedure
is an iterative process;
therefore, generating a
matching recipe within the
first cycle is an excellent
result.
[1] AJM deCraen, PJ. Roos, AL. deVries AL,
J. Kleijnen, Effect of color of drugs, BMJ,
313, pp 1624-1626 (1996)
[2] A.B.A. Overgaard, J. Møller Sonnergaard,
L.L. Christrup, J. Højsted, R. Hansen, Patients'
evaluation of shape, size and colour
of solid dosage forms, Pharmacy World &
Science Volume (23) 5, pp 185-188 (2001)
[3] A. Maschke, T. Schmeller, K. Kolter, Influence
of coating parameters on instant release
coated colored tablets, AAPS 2009
[4] V. Bühler, Kollicoat Grades Functional Polymers
for the pharmaceutical industry (2007)

TROUBLE-SHOOTING – FILM COATING
> If you have ever had the task of cleaning a
production-scale film coater, you are most probably
well aware of this problem: pigment residues
remaining in the tubes which carry the film coating
dispersion to the nozzle. With large-scale
coating equipment, this effect can be observed
quite frequently, leading to a number of problems
during the film coating process.
PROBLEM | The problem of deposition occurring
in the tubing is not so much the loss of pigments,
since the loss of material can be regarded
as being comparatively low. However, the impact
on the quality of the final product can be remarkably
high. Deposited pigments resistant to removal
by rinsing the tubing with water can flake
off the inner walls of the tubes and can cause
clogging of the nozzle and/or produce spots on
the core surface by depositing pigment agglomerates.
Both factors may result in unacceptable
quality of the tablets being coated.
The effect of sedimentation is described by
Stokes’s law (Equation 1), which states that the
sedimentation velocity (vs) depends on the size
of a given particle (dp), the difference between the
densities of the pigments (ρp) and the liquid carrier
(ρl), gravity (g) and viscosity (η).
A closer look at Stokes’s law indicates that the
film-forming characteristics of the polymers
should also be taken into consideration. In a typical
instant-release coating formulation, the type
of polymer and its concentration mainly determine
the viscosity of the dispersion.
No. 24, 2010
Trouble-Shooting in Film Coating: Deposition and Sedimentation
T. Cech, F. Wildschek
EQUATION 1 Stokes´s law
Excipients & Actives for Pharma
V s =
d 2 ·
p (ρp – ρl) · g
18 · η
log dynamic viscosity [mPas]
10000
1000
100
10
1
+ x
0
Polymer concentration [%]
x HPMC 3 mPas HPMC 6 mPas + HPC EF PVA Kollicoat IR Kollicoat Protect
FIGURE 2 Dynamic viscosity as a function of polymer content
Figure 2 shows the dynamic viscosity of typical
water-soluble instant release film coating polymers.
It can be seen that modern film formers like
polyvinyl alcohol (PVA), Kollicoat IR and Kollicoat
Protect have low viscosities. This enables the operator
to use a high concentration of solid matter
in the dispersion, thereby shortening the process
time. With regard to moisture-protective coatings
when high amounts of solids and small amounts
of polymer are recommended to optimize the
barrier effect, viscosity plays a crucial role 1 . If the
viscosity is too low, a tendency towards stronger
sedimentation can be observed.
Furthermore, polymeric dispersions such as
water-insoluble polymers emulsified in water (e.g.
Kollicoat SR 30 D) are sensitive with regard to
sedimentation; this is because the polymer does
not dissolve in the liquid carrier and therefore
does not contribute to increasing the viscosity.
Sedimentation due to low viscosity can be
+
x
+
x
+
x
5 10 15 20 25
prevented in the vessel containing the dispersion
by continuous stirring. However, stirring does not
solve the deposition issue in the tubing.
SOLUTION | According to Stokes’s law, particle
size (dp) to the power of two is the variable with
the highest impact on sedimentation. This high
impact of particle size on the sedimentation velocity
can be used for reducing the tendency to
sediment by selecting finer particles which are
not as prone to quick deposition.
Particle size
Specific density
Talc Kaolin
10 - 20 µm
2.58 - 2.83 g/mL
0.5 - 1.0 µm
2.61 - 2.68 g/mL
TABLE 1 Characteristic values for talc and kaolin particles
x
x
Page 15

Distribution [%]
FIGURE 3 PSD of film coating dispersions based on different polymers
One pigment used quite often in film coating formulations
is talc. An alternative additive similar in
characteristics and fields of application but of
considerably smaller particle size is kaolin (Table
1, Figures 3, 4 and 5).
Comparing the particles size distribution (PSD) of
film coating dispersions containing either talc or
Page 16
10
8
6
4
2
0
Excipients & Actives for Pharma
0.01 0.1 1 10 100
1000 10000
Log.particle size [µm]
FIGURE 4 SEM of talc FIGURE 5 SEM of kaolin
Kaolin (Kollicoat ® IR White)
Talc (HPMC-based)
Talc (PVA-based)
kaolin shows that kaolin shifts the PSD to smaller
values, thereby reducing the sedimentation tendency
considerably (Figure 3). This is why this excipient
is used in BASF's ready-to-use coatings.
Alternatively, a thickening agent can be used for
preventing sedimentation. A reduction in sedimentation
can also be achieved by increasing
No. 24, 2010
both the density of the liquid carrier and its
viscosity. However, the effect is less noticeable
and increasing viscosity influences the coating
process itself, leading to longer process times
and negative effects such as bridging and orange
peel.
In any case, deposition cannot be avoided
completely. In view of this, we can make some
practical recommendations on how to limit sedimentation
effects to a minimum:
� Use tubes with an inner diameter commensurate
with both spray rate and viscosity.
� Always keep the tubing as short as possible.
� As sedimentation mainly occurs in areas
where the tubing is horizontal, align the tubing
preferably vertically.
� If sedimentation starts to occur, reduce the
amount of deposited material at an early
stage by gently squeezing the tubing with
your fingers.
� Try to keep the pump running continuously
and stop spraying only if really necessary,
as, during movement, the degree of dispersion
sedimentation is always lower.
Taking all these points into account, undesired
problems such as gun blockage, bridging or colored
spots on the film-coated tablets can be substantially
reduced. |
REFERENCES
[1] Agnese, T., Cech, T., Kolter, K.; Developing
an instant release moisture protective coating
formulation based on Kollicoat Protect as
film forming polymer; PBP World Meeting;
April 7-10, 2008; Barcelona, Spain
[2] Kibbe, A. H.; Handbook of Pharmaceutical
Excipients; Pharmaceutical Press; 2000;
London, U.K.

ENDURING QUALITY
PVP (polyvinylpyrrolidone): An All-Round Talent with Tradition
C. Easterbrook, S. Hoefer
Library picture featuring old packaging
Excipients & Actives for Pharma
PVP and its derivatives in pharmaceutical
production
PVP - also known under the compendial name
"povidone" - has a long tradition at BASF and is
one of the most interesting and versatile polymers
used in the pharmaceutical industry. It helps
many of our customers to be even more successful.
Under the registered trade name Kollidon ® >
, PVP
is mainly used in tablets as a binder and disintegrant.
It thus makes the tablet a true high-tech
product: as a binder, it enables the individual active
ingredients of a tablet to form a homogenous
entity and as a disintegrant it ensures that the
tablets break up in liquid and release the active
ingredient quickly.
Quality and patient safety with PVP from BASF
Recently, BASF introduced a new plastic film as
primary packaging and BASF has applied for a
patent regarding this new packaging system. This
film is designed to protect BASF’s pharmaceutical
excipient polyvinylpyrrolidone (PVP) even better
against atmospheric oxygen and thus against
oxidation. This new and innovative packaging
raises product quality and thus improves patient
safety.
BASF's new and innovative
packaging raises
product quality and thus
improves patient safety.
The highest possible quality standards are required
for pharmaceutical applications. BASF’s
products, processes and facilities in fact exceed
the strict international quality standards of the
pharmaceutical industry. Consequently, the
United States Pharmacopeia (USP), an independent
work of reference, has certified the PVP produced
by BASF. Prior to certification, the USP
checked not only compliance with the requirements
of current Good Manufacturing Practice
(cGMP), but also the quality and the documentation
of production and quality control. At the
same time, the PVP marketed by BASF was also
certified for the European market subsequent to
a wide-ranging GMP audit. BASF guarantees a
consistently high product quality and in this way
contributes to the success of its pharmaceutical
customers. Recently, International Pharmaceutical
Excipients Auditing (IPEA) confirmed the
excellent quality of BASF’s PVP pharma grades.
BASF as well as other established PVP manufacturers
fulfill all requirements of the relevant
compendia. Read more on the importance of
No. 24, 2010
adequate supplier qualification in “Pharmaceutical
Technology” Volume 33 No. 10 pp. 84-88 (October
2009). The information is also accessible
under www.kollidon.de.
70 years of tradition in PVP production
PVP is a product that has been a real success
story. About 70 years ago, at the beginning of
1939, the chemist Walter Reppe, working in a
BASF laboratory in Ludwigshafen, patented
the production process for the polymer
polyvinylpyrrolidone. It quickly became clear that
the BASF researcher had discovered a veritable
all-rounder: PVP, although soluble in water, can
also absorb large quantities of water. It is nonirritating
to the skin and does not pose a health
hazard. It is also temperature-resistant, pH-stable,
non-ionic and colorless. Due to these varied features,
PVP can be used in a wide range of applications.
Even today, new opportunities continue to
be found. This makes PVP an all-round talent that
has a firm place in the BASF product portfolio. |
Page 17

New BASF CEPs with an extended retested period
� Certificates of suitability – a benefit for
our customers
As a manufacturer of active ingredients and
excipients, BASF has applied for certificates
concerning the evaluation of the suitability
of the monograph for the control of
the chemical purity and microbiological
quality of the substances – the CEP. The
certification procedure was established in
1994. To date BASF holds more than 30
CEPs, guaranteeing the quality of their
active ingredients and confirming that these
substances comply with the European Pharmacopoeia
and hence the requirements of
EU Directives for medicines.
CEPs are recognized by all Member States
of the European Pharmacopoeia Convention
as well as by other countries such as
Canada, Australia, New Zealand, Tunisia
and Morocco.
The CEP facilitates the management of our
customers’ applications for Marketing Authorization
for drugs in all these countries.
A retest period mentioned on the CEP
Page 18
UPDATE ON REGULATORY
AFFAIRS
D. C. Kriha, C. Becker
Substance CEP # New retest
period
[months]
Aminophylline anhydrous/
Theophylline-ethylenediamine
Aminophylline hydrous/
Theophylline-ethylenediamine hydrate
Caffeine
Dopamine hydrochloride
Excipients & Actives for Pharma
Dobutamine hydrochloride
Oxymetazoline hydrochloride
Tilidine hydrochloride hemihydrate
Xylometazoline hydrochloride
2007-288
2007-289
1998-022
2007-049
2006-273
2008-064
2007-045
2006-286
18
18
60
18
60
36
36
48
Monograph #
(Ph. Eur.)
300
301
267
664
1200
943
1767
1162
means that the results of stability studies
have been supplied to and assessed by the
EDQM, the European Directorate for the
Quality of Medicines & HealthCare, responsible
for the evaluation of CEP applications.
As a reliable partner to the pharmaceutical
industry, BASF continuously carries out stability
studies for all its APIs and excipients
in accordance with relevant ICH Guidelines.
Through the submission of complementary
and additional stability data, the retest period
of many products could be extended
over the past year – a benefit for pharmaceutical
companies and a further step to
help our customers to be even more successful.
� New US DMF Kollicoat ® IR Coating
Systems, DMF #23187
BASF has developed colored coating systems
for instant-release film-coating based
on Kollicoat IR, a water-soluble film former
for the instant-release coating of pharmaceutical
dosage forms. BASF offers seven
No. 24, 2010
basic colors, which can be combined to
achieve a wide variety of different color
shades. To support the formulation, development
software has been programmed to
predict the blend of basic colors required to
achieve the desired color shade.
� New US DMF phenylephrine
hydrochloride, DMF #23083
Phenylephrine is an effective decongestant
for treating allergic and cold indications.
With the launch of this well-established substance,
BASF is further extending its API
portfolio. As it is produced under cGMP
conditions, BASF is focusing on reliable and
consistent product quality in line with the
highest international quality standards.
� Soluplus ®
A Type IV DMF containing information on
chemistry, manufacture and control has
been filed with the FDA. DMF number assigned:
#23504. A Type V DMF containing
pre-clinical safety information has also been
filed. DMF number assigned: #23626.
� Solutol ® HS 15
In addition to the Type IV DMF (#9501)
which is already available, a Type V DMF
containing pre-clinical safety information
has been filed with the FDA. DMF number
assigned: #23531. A Solutol HS 15 monograph
titled "Polyoxyl 15 hydroxystearate”
will be published in USP 33-NF 28, which
becomes official as of October 2010.
Solutol HS 15 is a solubilizer for hardly soluble
APIs. Solubility is a prerequisite for
BCS class 2 and class 4 chemical entities to
be successfully formulated into pharmaceutical
dosage forms. Although no FDA-registered
formulations and thus market
approvals for finished medicinal products
containing Solutol HS 15 exist on the US

Pharma Ingredients & Services. Welcome to more opportunities.
Custom Synthesis | Excipients | Active Ingredients
Kollicoat ® IR Coating Systems
Create Your Own Colors.
Dr. Thorsten Schmeller
an enabler in excipients
Excipients & Actives for Pharma
market, the monograph was developed and
approved. This was driven by the Novel Excipient
Safety Evaluation Procedure that
IPEC Americas developed with input from
the FDA, clinical trial data from Wyeth and
safety evidence from BASF.
� Kollicoat IR
A revised draft EP Monograph “Macrogol
Poly (vinyl alcohol) grafted copolymer” will
be published in the next Pharmeuropa. In
the meantime, the monograph in Supplement
6.7 remains valid. USP-NF monograph
“Ethylene Glycol and Polyvinyl
Alcohol Graft Copolymer” is included in the
First Supplement to USP 33-NF 28, which
becomes official as of October 2010.
A draft JPE monograph (harmonized with
NEW MARKETING ASSETS
Kollicoat IR Coating Systems
Now everyone can create their own color simply
and cost-effectively. This new ready-to-use system
for colored coatings makes the production
of tablet coatings faster, more flexible, and more
robust than ever before. Kollicoat IR Coating Systems
have excellent flow properties and can be
re-dispersed quickly and easily. The seven glo-
the upcoming EP/USP-NF monographs) is
under preparation.
� Kollicoat MAE 100 P
A USP/NF monograph "Partially-Neutralized
Methacrylic Acid and Ethyl Acrylate Copolymer"
is adopted into the Second Supplement
to USP 33-NF 28, which becomes
official as of February 2011.
� Kollicoat SR 30 D
A new monograph for Kollicoat SR 30 D entitled
"Polyvinylacetate Dispersion" will be
published in the 2010 USP 33/NF28 edition.
Kollicoat SR 30 D is an aqueous polyinyl
acetate dispersion that was developed for
sustained release applications, where the
active ingredient is released independently
bally approved base colors can be combined to
create hundreds of shades. To download this
brochure, please use this link:
www.coating-systems.basf.com
Soluplus – The Solid Solution
This pioneering product overcomes the problem
of poorly soluble active ingredients and brings
bioavailability to a new level. Soluplus is unique in
many ways. Thanks to its high flowability and
excellent extrudability, Soluplus shows superior
performance in forming solid solutions, especially
in hot melt extrusion processes. It makes the
active pharmaceutical ingredient (API) available
in a dissolved state, resulting in improved bioavailability
once in the body. But that’s not all.
A comprehensive range of toxicological data
demonstrates the product’s safety. To download
this brochure, use the following link:
www.soluplus.com
Pharma Ingredients & Services. Welcome to more opportunities.
Excipients
Soluplus ® – The Solid Solution
Opening New Doors in Solubilization.
Dr. Shaukat Ali,
an enabler in excipients
No. 24, 2010
of the pH-value. It can be used as a film
coating agent and as a wet binder for matrix
tablets. A monograph for Kollicoat SR 30 D
is also included in the European Pharmacopoeia
("Poly(Vinyl Aceteate) Dispersion 30
Per Cent" #2152).
� Amylmetacresol
Amylmetacresol is a local antiseptic used to
treat minor infections of the mouth and
throat. OTC products containing amylmetacresol
are registered worldwide. The
draft EP monograph prepared by BASF in
collaboration with the EDQM has been
adopted by the European Pharmacopoeia
Commission, and becomes official in the
next supplement to EP. A CEP application is
already under preparation.
Page 19

July 10-14, 2010
The 37th Annual Meeting and Exposition
of the Controlled Release Society
Portland, Oregon, USA
October 5-7, 2010
CPhI Worldwide
Paris Nord Villepinte
Paris, France
November 14-18, 2010
AAPS Annual Meeting and Exposition
New Orleans, Louisiana, USA
December 1-3, 2010
CPhI India
Bombay Exibition Centre
Mumbai, India
Excipients & Actives for Pharma No. 24, 2010
CALENDAR PREVIEW
Influence of Various Plasticizers on the
Properties of a Kollicoat ® SR 30 D-Based
Coating
Our next Trouble-Shooting column will bring an interesting and helpful study on plasticizers used in film
coating formulations. Since plasticizers play a decisive role in the application of functional coats, it is
essential to have reliable recommendations for formulators.
The choice of a suitable plasticizer shows positive effects on the relevant processing properties of the
polymer, such as flexibility and minimum film forming temperature. Look out for this article in our next
edition and learn more about plasticizers application in film coating formulations!
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