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The application of Kollicoat IR as a
‘Zero Peroxide’ Binder for use in Solid Oral
Dosage Forms
ExcipientFest Nigel Langley
Kollicoat IR
Focus on Excipient Functionality
Market Need Platforms
2
Solubilization Softgels Biologics Solutions
Instant & Modified Release
Skin Delivery
.
Focus on Excipient Functionality
Market Need Platforms
3
Solubilization Softgels Biologics Solutions
Instant & Modified Release
Skin Delivery
Kollicoat IR
Instant Release
Coating Polymer
.
Kollicoat IR - Elongation at Break
4
Kollicoat IR® Impact of Viscosity on processing steps
Preparation of the coating suspension Film coating Process
5
Kollicoat IR’s low viscosity over all leads to a shortened process time and an increase of
production efficiency (through-put) through all these factors
01.02.2016
Process Parameter for IR Film Coating Kollicoat IR
formed film is very
flexible
extremely wide
range of usable
parameters
very short
process time
clearly separated
quality zones
25 75 125 175 225 275
15
20
25
30
35
40
45
50
PROCESS TIME [minutes]
PR
OD
UC
T T
EM
PE
RA
TU
RE
[°C
]
film coating impossible, sticking of the cores optimum film coating process, surface acceptable
film coating principally possible, surface not acceptable optimum film coating process, best results in surface quality
Process Parameter for IR Film Coating
Comparison to Competitor Products
film coating impossible, sticking of the cores optimum film coating process, surface acceptable
film coating principally possible, surface not acceptable optimum film coating process, best results in surface quality
Properties of the isolated Films
Pigment Binding Capacity
0
20
40
60
80
100
120
140
160
180
0 10 20 30 40 50 60 70 80
elo
ng
ati
on
at
bre
ak
[%
]
.
talc concentration [%]
Kollicoat IR
HPMC type 3 mPas
HPMC type 6 mPas
Focus on Excipient Functionality
Market Need Platforms
9
Solubilization Softgels Biologics Solutions
Instant & Modified Release
Skin Delivery
Kollicoat IR
Instant Release
Coating Polymer
Wet Binder
.
Kollicoat® IR Instant release binder options from BASF
10
Granulation
Dry (roller
compaction) Wet
Kollidon VA64 Fine
Kollidon CL-M
Kollidon VA64
Aqueous Solvent-
based
Low volume,
high binding
Kollidon 90
Peroxeal
Kollicoat IR
K30 LP Peroxeal
K25 / K30 Peroxeal
Maximum
protection
Superior
protection
Extended
protection
Peroxides
Kollidon VA64
Kollidon CL-SF
Direct
compression
Ludiflash
Regular ODT
Ludipress
CL-M
VA64 Fine
Ready-to-use
VA64
Kollicoat® IR Market trend towards the use of low-peroxide binders
11
Need for low peroxide
formulations
New sensitive APIs
Low dosage
formulations
Product lifecycle
mgmt
OTC packaging (no
blister)
Cost efficiency
Examples for peroxide-
sensitive APIs
Hormones
Estrogen
Gestagen
Antivirals / Anti-HIV
Saquinavir
Coronary
Verapamil
Diltiazem
Peroxide Kollicoat® IR does not show peroxide buildup!
12
Batch No Peroxide level,
meq/kg* at release
21686… <1
08838… <1
84490… <1
70814… <1
11672… <1
26376… <1
88474… <1
39781… <1
68529… <1
21772… <1
Months at
40°C/75% r.h.
Peroxide level,
meq/kg*
0 month <1
3 months < 1
6 months < 1
12 months 1
18 months 1
30 months 1
After production During stability storage
13 10.12.2015
Chemical Structure
Graft polymer –
consisting of PEG 6000 and Polyvinyl alcohol
Spray dried product
Molecular weight approx. 45.000 Dalton
pH-Value 5 to 8 (solution 20% solids)
Kollicoat IR
Viscosity Kollicoat IR, Kollidon 25, 30, VA64 & solutions can be
processed with acceptable low viscosities
14
1,E+00
1,E+01
1,E+02
1,E+03
1,E+04
1,E+05
1,E+06
1,E+07
0 5 10 15 20 25 30 35
Lo
g.
dyn
am
ic v
iss
co
ss
ity [
mP
as
]
Polymer content [%]
Kollidon® 25 Kollidon® 30 Kollidon® 90F Kollidon® VA64
HPMC 3 mPas HPMC 6 mPas HPMC 15 mPas Kollicoat® IR
Viscosity of binder solutions Batch size: 400g
Water: 50g
Polymer (solution): 6g ► 10.7%
12g ► 19.4%
20g ► 28.6%
Polymer (granules): 1.5% ► 6g
3.0% ► 12g
5.0% ► 20g
Kollicoat® IR. Processability in fluid bed and high shear granulation
15
Granulation
Dry
granulation
Roller
compaction Melt granulation Extrusion Fluid bed*
Top spray
Bottom spray Low shear
High shear
Vertical
granulation
Wet
granulation
*applicable as binder solution or using water for powder-blends
0
2
4
6
8
5 kN 10 kN 18 kN
Kollicoat® IR In fluid bed granulation, Kollicoat IR shows outstanding tensile
strength at low binder content*
16
Tablets with 10% Binder Tablets with 20% Binder**
*formulated with Ca-Phosphate as filler
**HPMC 6mPas hardly processable in high-shear granulation due to impact of high viscosity
Tensile Strength [N/mm²]
0
2
4
6
8
5 kN 10 kN 18 kN
Kollidon 30 (Batch A)
Kollidon 30 (Batch B)
Kollicoat IR
HPMC 6 mPas
Tensile Strength [N/mm²]
Kollicoat
IR
Kollicoat® IR In high-shear granulation, Kollicoat IR performs comparable to PVP
17
With 10 kN compression force** With 18 kN compression force**
*formulated with Ca-Phosphate as filler
**HPMC 6mPas hardly processable in high-shear granulation due to impact of high viscosity
0
2
4
6
8
Kollidon K30(Batch A)
Kollidon K30(Batch B)
Kollicoat IR0
2
4
6
8
Kollidon K30(Batch A)
Kollidon K30(Batch B)
Kollicoat IR
Tensile Strength [N/mm²] Tensile Strength [N/mm²]
Kollicoat® IR API release comparable to PVP
18
0
20
40
60
80
100
0 20 40 60 80 100 120
Dru
g r
ele
as
e [
%]
Time [min]
Fluid bed granulation with 20% Binder
0
20
40
60
80
100
0 20 40 60 80 100 120
Dru
g r
ele
as
e [
%]
Time [min]
Kollidon 30
Kollidon 30
Kollicoat IR
HPMC 6mPas
Fluid bed granulation with 10% Binder
HPMC 6mPas not
processable as granulation
liquid to viscous
19
Sr. No Ingredients 3% binder 6% binder
mg/tab % content mg/tab % content
1 Raloxifene hydrochloride 60 30 60 30
2 Binder 6 3 12 6
3 DCP (Calipharma A) 128 64 122 61
4 Aerosil 200 4 2 4 2
5 Magnesium Stearate 2 1 2 1
Total 200 100 200 100
Kollicoat® IR No API degradation products formed
Binder type/-quantity Unit Initial 1 month 3 month 6 month
Kollicoat IR - 6%
area-%
0 0 0 0
Kollidon 30 LP - 6% 0 0 0 0
Competitor Povidone - 6% 0 0.02 0.02 0.02
Competitor product - 6% 0 0.02 0.02 0.02
Degradation products of Raloxifene in stability (Raloxifene-N-oxide)
Formulation
Kollicoat® IR Allows peroxide-free binding using low binder content with a
wide processing window
20
0 1 2 3 4 5 6 7 8 9 10
.
VA-VP
HPMC 15mPas
HPMC 6mPas
HPMC 3mPas
PVP K90
PVP K30
PVP K25
Recommended binder content [%]
better results worse results
better worse
Kollicoat IR
Kollicoat IR is one of the binders where a minimum of
binder content is optimal for the granulation.
Kollicoat® IR Is peroxide free along the full lifecycle
21
Kollidon
25/30/90F
… in Peroxeal
Kollidon 30 LP in Peroxeal
Kollicoat IR
Closed/resealed Whole lifetime Open Sealed
Excipient Finished dose
Kollicoat® IR Is solely suited for aqueous wet binding
22 .
Functionality Kollicoat® IR – Powerful binding. No peroxides.
23
Cellulose
derivatives
Native
starch
Kollidon
25 / 30
Kollidon
90F
Kollicoat
IR
Peroxides
Viscosity ( aq. solution)
Binding power
Processing window
Pre-processing
Organic solvents
low
high
wide
no
yes
yes
high
very high
wide
no
yes
yes
medium/high
medium
small
no
yes
no
high
medium
small
yes
no
no
low
high
wide
no
no
no
Kollicoat IR has the benefits of PVP and cellulosic derivatives in 1 Binder
Kollicoat IR FDA Inactive Ingredient Database , IID
Inactive
Ingredient Route Dosage Form CAS Number UNII
Maximum
Potency
POLYVINYL
ALCOHOL
GRAFT
POLYETHYLENE
GLYCOL
COPOLYMER
(3:1; 45000 MW)
ORAL TABLET 121786161 23ZQ42JZZH 5.37MG
POLYVINYL
ALCOHOL
GRAFT
POLYETHYLENE
GLYCOL
COPOLYMER
(3:1; 45000 MW)
ORAL TABLET,
EXTENDED
RELEASE
121786161 23ZQ42JZZH 19MG
24
Regulatory Kollicoat® IR – Powerful binding. No peroxides.
25
US –self-affirmed GRAS
Pharma Dietary supplements
Europe - Use as binder in
food supplements covered by
E1209
Ph.Eur (EU)
USP/NF (USA)
JPE (Japan)
TGA (Australia)
Summary Kollicoat® IR – Powerful binding. No peroxides.
26
Binding performance at least as good as Kollidon 30
No evidence for peroxide formation at any time
Binding power
No peroxide
formation
Easy processing due to low viscosity in solution Low viscosity
What’s next?
Kollicoat IR Fine - In development – Low peroxide dry binder
