Kollicoat Smartseal 30 D Short

The first aqueous polymer dispersion for
taste masking & moisture protection

Kollicoat

Smartseal 30 D
Active Protection.
Pharma Ingredients & Services
Customer presentation December 2010
October 2010
Kollicoat Smartseal 30 D - Technical presentation
2
Kollicoat

Smartseal 30 D
Content
Introduction
Functionalities & applications
Application data
Regulatory information & toxicological data
Packaging & storage information
Summary
October 2010
3
Kollicoat

Smartseal 30 D
Content
Application data
Summary
Introduction
October 2010
4
Kollicoat

Smartseal 30 D
Formulation needs moisture protection
Any solid dosage form that is exposed to humidity will take up moisture
Some active ingredients or certain types of dosage forms (e.g. formulations
with a disintegrant or matrix tablets) are particularly sensitive to moisture.
Moisture uptake during the packaging process or after dispensing the drug
product must be reduced to preserve the efficacy of sensitive actives.
October 2010
5
Many active ingredients exhibit a specific taste. Very often they are bitter.
Orally disintegrating tablets or sprinkles, which are easier to dose and more
convenient to apply, can help to improve compliance in various patient
groups.
Taste masking has gained particular importance with the increasing
popularity of orally disintegrating tablets and the need to develop
pediatric medicines.
Pellet coating Tablet coating Particle coating
Kollicoat

Smartseal 30 D
Formulation needs taste masking
October 2010
6
Kollicoat

Smartseal 30 D
Desired functionality of protective coatings
Low water permeability
& high stability in saliva
Quick dissolution
& drug release in the
stomach
Lipophilic polymer with a defined number of
basic functional groups
Effective protection from moisture or
unpleasant taste
pH 7
pH1-5
October 2010
7
Kollicoat

Smartseal 30 D
Content
Introduction
Application data
Summary
October 2010
8
Kollicoat

Smartseal 30 D
Polymer structure
Methyl methacrylate diethylaminoethyl methacrylate copolymer (6:4)
The polymer is insoluble at basic and
neutral pH-values
At pH-values below 5.5, the polymer
dissolves quickly under salt formation
Basic functional
groups
The lipophilic polymer is insoluble in the saliva (pH 6.8-7.2) and
dissolves quickly in the acidic environment of the stomach.
October 2010
9
Kollicoat

Smartseal 30 D
Product form & composition
Kollicoat
Smartseal 30 D [methyl methacrylate -

diethylaminoethyl methacrylate copolymer
dispersion] is an aqueous polymer dispersion
with a solids content of approx. 30 %.
It contains approx. 0.6% macrogol cetostearylether 20
and approximately 0.8% sodium laurylsulfate as
stabilizers.
Kollicoat
Smartseal 30 D is a milky white liquid with a faint

characteristic and pleasant odor.
October 2010
10
Kollicoat

Smartseal 30 D
Product characteristics
Parameter Kollicoat
Smartseal 30 D
Molecular weight ~ 200 000 dalton
Viscosity 2-50 mPas
Particle size Approx. 150 nm (laser scattering)
pH-Value 7.5-10.0
Residual monomers max. 100 ppm
Minimum film forming temperature (MFT) Approx. 57C
Glass transition temperature (Tg) 57C
Water cannot act as plasticizer within the lipophilic polymer.
Consequently, the measured MFT of Kollicoat
Smartseal 30 D is higher
than of other well known polymer dispersions.
October 2010
11
Kollicoat

Smartseal 30 D
Solubility
0
1
2
3
4
5
6
7
8
9
10
0 2 4 6 8 10 12 14
1 mol/l HCl [ml]
p
H
clear solution
Neutralization curve of the diluted dispersion (50 g; 10% solids content)
The addition of hydrochloric acid leads to the formation of a polymeric
buffer system. At values of pH 5.5 and below, the polymer dissolves
and the milky white dispersion turns into a clear solution.
October 2010
12
Kollicoat

Smartseal 30 D
Sorption isotherm
0
10
20
30
40
50
60
70
80
90
100
30 40 50 60 70 80 90 100
Rel. humidity [%]
Sorption
Desorption
W
a
t
e
r

c
o
n
t
e
n
t
[
%
]
The complete insensitivity to moisture determines the effective
barrier function.
October 2010
13
Kollicoat

Smartseal 30 D
Selection of a plasticizer
Due to the methyl- methacrylic moiety the copolymer is relatively
hard and brittle. Several plasticizers can be used in combination with
Kollicoat
Smartseal 30 D.
Recommended plasticizers
Optimal concentration:
13 15% w/w
(calculated on the polymer)
Tributyl citrate (TBC)
Triethyl citrate (TEC)
Acetyltriethyl citrate (ATEC)
Acetyltributyl citrate/ docusate
sodium (ATBC/DS)
Dibutyl sebacate/ docusate sodium
(DBS/ DS )
October 2010
14
Kollicoat

Smartseal 30 D
Addition of an antioxidant
Antioxidants are required to stabilize the aminoester moiety and
thereby dissolution behavior and reduce yellowing under stress
conditions.
Butylated hydroxytoluene (BHT)
N-acetylcysteine
1 - 2.5% related to polymer
1 - 2.5% related to polymer
October 2010
15
Kollicoat

Smartseal 30 D
Formulation recommendations
Plasticizer
TBC, ATEC, TEC, ATBC/DS, DBS/DS
Antioxidant
BHT
Pigments
Talc
Colorants
13 -15 %
related to polymer
1 - 2.5 %
related to polymer
0 - 50%
based on total film mass
2 10%
based on total film mass
Antioxidants are required to stabilize tablet coatings. BHT is the first choice.
Pigments are particularly important for moisture barrier formulations.
Talc shows the best results.
October 2010
16
Kollicoat

Smartseal 30 D
Preparation of the coating suspension
Pigments
T
E
C

&
B
H
T
P
la
s
t
ic
is
e
r
1
2
K
o
l
l
i
c
o
a
t
Plasticizer & additives

Pigments
Source: http://upload.wikimedia.org/wikipedia/commons/thumb/3/33/Becherglas.svg/220px-Becherglas.svg.png
http://www.schule-bw.de/unterricht/faecher/chemie/material/unter/einf_pics/bild1.jpg
Dissolve the lipophilic antioxidants
(BHT) in the plasticizer.
Elevated temperatures ( ~50C)
speed up the process.
Disperse pigments in water
with a high shear mixer (10 min).
Hydrophilic antioxidants can be
added.
Add Kollicoat Smartseal 30 D
to the pigment suspension
Add the plasticizer (with additives)
Stirr for 2 hours.
Pass through a 200 m sieve
Step 1 Step 2 Step 3
Kollicoat
Smartseal 30 D and plasticizer are added into the pigment

suspension. Stirring for 2 hours is necessary to incorporate the
plasticizer into the polymer droplets.
October 2010
17
Kollicoat

Smartseal 30 D
Handling recommendations
Exposure to frost
Addition of acidic ingredients should be avoided because of
potential interactions with the functional groups of the
polymer
As with all aqueous polymer dispersions some factors could result in an
irreversible coagulation that precludes further use of the product:
Kollicoat
Smartseal 30 D is comparably stable so that it is possible

to add the recommended plasticizers directly and without prior
dilution into the dispersion.
October 2010
18
Kollicoat

Smartseal 30 D
Cleaning recommendations
Aqueous solutions of acetic acid, formic acid or citric acid
Commercially available cleaning agents
As the polymer is readily soluble in acidic solutions, acidic preparations are
recommended as cleaning agents:
Coating equipment can be cleaned easily from residues of
Kollicoat
Smartseal 30 D based formulations.

October 2010
19
Kollicoat

Smartseal 30 D
Impact of the plasticizer concentration
Minimum film forming temperature (MFT)
The minimum film forming temperature (MFT) can be reduced
by the addition of a plasticizer.
0
10
20
30
40
50
60
0 5 10 13 15 20
Concentration of plasticizer and surfactant [% rel.to polymer]
M
i
n
i
m
u
m

f
i
l
m

f
o
r
m
i
n
g

t
e
m
p
e
r
a
t
u
r
e
[
C
]
Tributyl citrate
Acetyltriethyl citrate
Triethyl citrate
Acetlytributyl citrat +Docusate sodium 2%
Dibutyl sebacate +Docusate sodium 2%
recommended level
October 2010
20
Kollicoat

Smartseal 30 D
Impact of the plasticizer concentration
mechanical properties
Plasticizer content rel. to polymer [%]
E
l
o
n
g
a
t
i
o
n

a
t

b
r
e
a
k

[
%
]
The elasticity of polymer films can be increased by the addition of
plasticizers.
0
50
100
150
200
250
300
10 15 20 25
Triethyl citrate
Tributyl citrate
Acetyltriethyl citrate
casted films
recommended level
October 2010
21
Kollicoat

Smartseal 30 D
Content
Introduction
Summary
Application data
October 2010
22
Applications
Tablet
coating
Pellet
coating
Subcoating
Taste masking
for oral
dispersibles
Particle
coating
Rumen stable
DDS
Recommended coating levels:
Taste masking: 2 5 mg/cm
Moisture barrier: 5 20 mg/cm
Granulation
October 2010
23
Kollicoat

Smartseal 30 D
Application data
Sorbitol tablets (moisture protection)
Acetaminophen crystals
Caffeine pellets
Theophylline granules
Caffeine tablets (taste masking)
Process parameter charts
Quinine hydrochloride tablets (taste masking)
October 2010
24
Kollicoat

Smartseal 30 D
Application data
Caffeine pellets
October 2010
25
Kollicoat

Smartseal 30 D
Caffeine tablets: core formulation
Caffeine 100 mg
Ludipress
189 mg
Avicel
PH 101 40 mg
Magnesium stearate 1 mg
Total weight 330 mg
Tablet shape: round, diameter 9 mm, convex
October 2010
26
Kollicoat

Smartseal 30 D
Caffeine tablets: Process parameters
Machine Accela Cota, 24
Inlet air temperature 60C
Batch size 7 kg
Product temperature 30 33C
Spraying rate 35 g/min
Nozzle diameter 1mm
Spray pressure 1.5 bar
Final drying 45C (product temperature)
Coating level 4.5 mg/ cm ~2.8% weight gain
October 2010
27
Kollicoat

Smartseal 30 D
Caffeine tablets: Dissolution at pH 6.8
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time [min]
D
r
u
g

r
e
l
e
a
s
e

[
%
]
1mg/cm coating level
uncoated core
A coating level of 4 mg/cm prevents caffeine dissolution at pH 6.8 for
more than 60 minutes.
October 2010
28
Kollicoat

Smartseal 30 D
Caffeine is released quickly and completely at pH 1.2.
0
20
40
60
80
100
120
0 10 20 30 40 50 60
Time [min]
D
r
u
g

r
e
l
e
a
s
e

[
%
]
1 mg/cm coating level
uncoated cores
October 2010
29
Kollicoat

Smartseal 30 D
0
20
40
60
80
100
120
0,00 10,00 20,00 30,00 40,00 50,00 60,00
Time [min]
D
r
u
g

r
e
l
e
a
s
e

[
%
]
Kollicoat Smartseal 30 D based formulation
Basic butylated methacrylate copolymer
based formulation
HPMC based coating system
uncoated core
A coating level of 4 mg/cm Kollicoat
Smartseal 30 D can prevent

dissolution from caffeine tablets than other well known protective coatings.
October 2010
30
Kollicoat

Smartseal 30 D
Caffeine tablets: Taste masking effect
0
2
4
6
8
3 mg/cm 4 mg/cm 5 mg/cm
*Number of individuals who reported a bitter taste when putting coated Caffeine (100 mg) tablets into
the cheek (7 test persons)
N
u
m
b
e
r
o
f

b
i
t
t
e
r

s
e
n
s
a
t
i
o
n
s
*
Kollicoat Smartseal 30 D
Basic butylated methacrylate
copolymer based formulation
HPMC based system
Kollicoat
Smartseal 30 D can effectively mask the taste of caffeine tablets

at coating levels of of 4-5 mg/cm.
October 2010
31
Kollicoat

Smartseal 30 D
Application data
Caffeine pellets
October 2010
32
Kollicoat

Smartseal 30 D
The process parameter chart is a method to visualize the influence of
varying process parameters on film coating results.
It helps to compare the properties of a coating formulation and its
processabilty in varying equipment and scale.
p
r
o
d
u
c
t

t
e
m
p
e
r
a
t
u
r
e

[
C
]
Process time [min] =
[ ]
content matter solid
g
rate spray
gain weight g size batch
min
October 2010
33
Par amet er Sett ing
Machine Manesty XL Lab 01
Batch size 5 kg
Drum diameter 480 mm
Coating level 4.5 mg/cm
Drum speed 12
Exhaust air quantity 350 m/h
Atomising air pressure 1.5 bar
Flat jet air 0.75 bar
Kollicoat

Smartseal 30 D
Standard setting for process parameter chart
The design of experiment plan comprises 5-15 batches. It takes about
300 -450 points to create a process parameter chart.
October 2010
34
25 75 125 175 225 275
15
20
25
30
35
40
45
50
PROCESS TIME [ minut es]
P
R
O
D
U
C
T

T
E
M
P
E
R
A
T
U
R
E

[
C
]
Kollicoat

Smartseal 30 D
13% ATBC* / 2.5% BHT* 25% Talc
Film coating impossible;
sticking of the cores
Film coating principally possible
surface not acceptable
Optimal film coating process;
surface acceptable
best results in surface quality
Excellent film coating results can be achieved with a wide range of
operating parameters and short process times.
* Concentrations based on polymer weight
October 2010
35
25 75 125 175 225 275
15
20
25
30
35
40
45
50
PROCESS TIME [ minut es]
P
R
O
D
U
C
T

T
E
M
P
E
R
A
T
U
R
E

[
C
]
Film coating impossible;
sticking of the cores
Film coating principally possible
surface not acceptable
surface acceptable
best results in surface quality
Kollicoat Smartseal 30 D
Formulation: 13% TEC* / 2.5% BHT* / 40% Talc
Excellent film coating results can be achieved with an unusually
wide range of operating parameters, even at high spray rates.
* Concentrations based on polymer weight
October 2010
36
Kollicoat

Smartseal 30 D
Content
Introduction
Application data
Summary
October 2010
37
Kollicoat

Smartseal 30 D
Kollicoat Smartseal
30 D is a new excipient. There are no registered drug products

yet.
The pharmacokinetics and the pre-clinical safety of Kollicoat
Smartseal 30 D are
adequately documented by in vitro and in vivo studies that were in line with the
current international guidelines, regulations and recommendations.
In the US, there will be Type IV and Type V Drug Master Files for Kollicoat
Smartseal
30 D (filing is planned until end of 2010)

Tox Abstract and Tox Expert Report are available for Kollicoat
Smartseal 30 D.
BASF has successfully introduced several novel excipients to the market and we
will assist our customers who are in the process of filing.
October 2010
38
Kollicoat

Smartseal 30 D
Content
Introduction
Application data
Summary
October 2010
39
Kollicoat

Smartseal 30 D
Summary
The first water based polymer dispersion for
taste masking and moisture protection
Smart protection from unpleasant taste
Effective sealing against moisture
Fast release of active ingredients
Easy and economical film coating
www.kollicoat-smartseal.basf.com

Kollicoat Smartseal 30 D Short

Caricato da

Informazioni sul documento

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Kollicoat Smartseal 30 D Short

Caricato da

Copyright:

Formati disponibili

The first aqueous polymer dispersion for

taste masking & moisture protection

Smartseal 30 D [methyl methacrylate -

Smartseal 30 D is a milky white liquid with a faint

Plasticizer & additives

Smartseal 30 D and plasticizer are added into the pigment

Smartseal 30 D is comparably stable so that it is possible

Smartseal 30 D based formulations.

Smartseal 30 D can prevent

Smartseal 30 D can effectively mask the taste of caffeine tablets

30 D is a new excipient. There are no registered drug products

30 D (filing is planned until end of 2010)

Potrebbero piacerti anche