1
Evolution of EUDRAGIT®
Applications with the New
Technologies
-Options to Meet
Modern Therapeutic Needs
Dr. Brigitte Skalsky
Evonik Industries, Pharma Polymers
Barcelona, December 2, 2010
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 2
EUDRAGIT® polymers
and their applications
Enteric coatings
Insoluble in acidic media
Taste masking &
moisture protection
Soluble in gastric fluid /
fast disintegrating
Sustained release
Insoluble but permeable,
pH independent
EUDRAGIT® L- & S-Polymers EUDRAGIT® E-Polymer
EUDRAGIT® NE- & NM-Polymer EUDRAGIT® RL- & RS-Polymer
EUDRAGIT®
2
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 3
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 4
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
3
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 5
EUDRAGIT® polymers applications
in matrix formulations
RL PO, RS PO ���� time-control
L100, L 100-55 ���� pH-control
S100, ���� time-control
Roller compaction
RL PO, RS PO ���� time-control
L 100-55 L100 ���� pH-control
S100 ���� time-control
Direct compression
RL 100, RS 100, RL PO, RS PO ���� time-control
L 100-55 ���� pH-control
Hot melt
granulation / pelletization / extrusion
RL 100, RS 100, RLPO, RSPO ���� time-control
L 100-55, L100, L 12,5 ���� pH-control
S 12,5, S100 ���� time-control
Organic granulation / pelletization
RL 30 D, RS 30 D ���� time-control
NE 30 D, NE 40 D, NM 30 D ���� time-control
L 100-55, L 30 D-55, L100 ���� pH-control
S100 ���� time-control
Aqueous granulation / pelletization
EUDRAGIT® gradeProcess technology
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona
Anionic EUDRAGIT® types
in matrix applications
≥≥≥≥ pH 7.0FS 30 D
≥≥≥≥ pH 7.0BS 100
S 12,5
≥≥≥≥ pH 6.0AL 100
L 12,5
≥≥≥≥ pH 5.5CL 30 D-55
L 100-55
SolubilityMethacrylic Acid
Copolymer
USP/NF Type
EUDRAGIT®
Type
time controlled matrices
with S / FS under
physiological conditions
pH controlled matrices
4
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 7
Drug release from inert matrices –pH controlled with EUDRAGIT® L polymers
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 8
EUDRAGIT® L 30 D-55 matrix pH profile
35% Diltiazem, 20% polymer, fluid bed, 500mg tablet, 15 kN
0
10
2030
40
50
60
7080
90
100
0 60 120 180 240 300 360 420 480 540
Time (min)
% D
isso
lved
pH 1
pH 6
pH 6.8
pH 7.4
�EUDRAGIT® L 30 D-55 provides pH dependent release
5
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 9
Drug release from inert matrices –time controlled with EUDRAGIT® NE, NM, RL/RS, S, FS
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 10
0
10
20
30
40
50
60
70
80
90
100
0 60 120 180 240 300 360 420 480 540
Time (min)
% D
isso
lved
pH 1
pH 6
pH 6.8
���� EUDRAGIT® FS 30 D provides pH independent release
EUDRAGIT® FS 30 D matrix pH profile
35% Diltiazem, 20% polymer, fluid bed, 500mg tablet, 15 kN
6
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 11
Release Profile at pH=1.0
0102030405060708090100
0 100 200 300 400 500
Time [min]
%Dis
solv
ed
Aquacoat® ECD (20%)
Methocel® E5 (20%)
Methocel® K4M (20%)
Methocel® K15M(20%)
EUDRAGIT® NE 30D (20%)
EUDRAGIT® NE 30D (7.5%)
Release Profile at pH=6.8
0102030405060708090100
0 100 200 300 400 500
Time [min]
% D
issolv
ed
Aquacoat® ECD (20%)
Methocel® E5 (20%)
Methocel® K4M (20%)
Methocel® K15M (20%)
EUDRAGIT® NE 30D (20%)
EUDRAGIT® NE 30D (7.5%)
SR Potential of different matrix formers
• Retardation of Methocel
types depends on molecular
weight
• Methocel matrices show
some pH dependency
• 7.5% EUDRAGIT® NE
similar to 20% Aquacoat
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 12
���� Superior compressibility with EUDRAGIT® NE 30 D
0
50
100
150
200
Crushing
st rengt h ( N )
Aquacoat® ECD (20%) Methocel® E5 (20%) Methocel® K4M (20%) Methocel® K15M
(20%)
EUDRAGIT® NE 30D
(20%)
EUDRAGIT® NE 30D
(7.5%)
Compression f o rce ( 15kN )
Compressibility of different matrix formers
35% Diltiazem, 500mg tablet weight, fluid bed granulation
7
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 13
SR matrix pellets by melt extrusion
0
20
40
60
80
100
120
0 100 200 300 400 500 600 700 800
time t [min]
Dis
solu
tion T
heophyllin
[%
] RS(80)+RL(00)+Theophyllin(20)
RS(40)+RL(40)+Theophyllin(20)
RS(00)+RL(80)+Theophyllin(20)
RS(65)+RL(00)+Theophyllin(35)
RS(32,5)+RL(32,5)+Theophyllin(35)
RS(00)+RL(65)+Theophyllin(35)
RS(50)+RL(00)+Theophyllin(50)
RS(25)+RL(25)+Theophyllin(50)
RS(00)+RL(50)+Theophyllin(50)
pH 1.2 pH 6.8
RL PO only + Theophyllin
RL PO + RS PO + Theophyllin
RS PO only + Theophyllin
• round shaped Micro Spheres can be obtained by
an air-cooled hot-face cutting process
• the combination of EUDRAGIT® RL/RS gives a
high variability in dissolution kinetics
• optional coatings to add functionalities
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 14
Melt extrusion pellets from
LEISTRITZ Micro Pelletizer (1)
Extruder
Knife
Nozzle
Ring Nozzle Plate
Heat Sealing Cap
Extruder Screws
Polymer Melt
8
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 15
Melt extrusion pellets from
LEISTRITZ Micro Pelletizer (2)
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 16
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
9
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 17
Buproprion hydrochloride
BCS Classification : Class I
Solubility : High solubility i.e. 312 mg /ml in water,
193 mg/ml in alcohol,
333 mg/ml 0.1 N HCl (Merck Index).
Appearance : White crystalline powder, bitter in taste
Therapeutic class : Antidepressant
USP SPECIFICATIONS
Not less than 80%8
60 to 85 4
25 to 45 1
Drug released [%]Time [hours]
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 18
EUDRAGIT® FS 30 D matrix granulation –
top spray fluid bed
Dry Mixing
150Bupropion hydrochloride
15L-Cysteine hydrochloride
133Microcrystalline cellulose
Granulation
60EUDRAGIT® FS 30 D
(Solid Content)
Lubrication
24PVP K-90
16Glyceryl behenate
2Calcium stearate
400Total
Weight per tablet (mg)
10
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 19
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8
Time in hours
% Release of Bupropion HCl ± SD
Water
Buffer pH 1.2
Buffer pH 3.0
Buffer pH 4.5
Release of Bupropion independent from EUDRAGIT® FS matrix tablets
Robust drug release in different media
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 20
Storage stability
Final formula contains 15% w/w EUDRAGIT® FS 30 D per tablet
0
20
40
60
80
100
0 2 4 6 8Time in hours
%Release of Bupropion HCl + SD
Initial
3M 40ºC-75% RH
USP LOWER LIMITS
USP UPPER LIMITS
Tablet Hardness: 200-250 N, Friability: 0,1%
11
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 21
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 22
The EUDRACOL® design
EUDRAGIT® RL / RS layer
● Sustained release behaviour
varies with polymer ratio & film thickness
EUDRAGIT® FS layer
● Colon Targeting
a
Drug containing pellet
a) Sugar bead & layered drug (low drug loading)
b
b) Drug pellet (high drug loading)
12
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 23
How does EUDRACOL® work?
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 24
In-vivo proof of concept
A. EUDRACOLTM delivers drug along the colonic transit
B. IR Pellets delivers drug to the colon
C. IR Reference releases drug in stomach
Caffein
edis
solv
ed
[%]
In-vitro dissolution profiles
0
20
40
60
80
100
0
time [h]
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
0.1 N HCl
buffer pH 7.5
0 4 8 12 16 20 24
0
3
6
9
12
15
18
21
Human plasma profiles
time [h]
Seru
m level[µ
mol/L]
Arrival in colon t lag
13
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 25
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 26
CH2
C
C=O
CH3
CH2
C
C=O
H
OC2H5
CH2
C
C=O
CH3
OCH3 O
C2H4N
+(CH3)3Cl-
CH3COO-Na+
+CH3COO
-
C2H4N+(CH3)3
+
Na+Cl-
Ionic
Interaction
Modulated drug release based on
EUDRAGIT® RL/RS 30 D features
Increased permeability
by enhanced swelling
14
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 27
How does it work?Tailor made profiles based on EUDRAGIT® RL/RS + NE
Water
Controlled release of salt
Salts interacts with
outer polymer layer
Modulated Drug
Release
Initial diffusion
of drug
Slow-Quick Release
0
20
40
60
80
100
0 2 4 6 8 10 12 14
Zero-order Release
0
20
40
60
80
100
120
0 2 4 6 8 10 12 14
Accelerated Release
0
20
40
60
80
100
0 2 4 6 8 10 12 14
Quick-Slow Release
0
20
40
60
80
100
0 2 4 6 8 10 12 14
CR layer
EUDRAGIT® RL/RS
Modulating layer
EUDRAGIT® NE
Salt
Drug layer
1
2
3
4
5
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 28
0
20
40
60
80
100
0 2 4 6 8 10 12
Pellets containing different salts as cores and coated
with EUDRAGIT® RS as the controlled release layer
(20%w/w)
Time in hours
% T
heophyllin
e rele
ased
Acetate
Citrate
Succinate
Chloride
0
20
40
60
80
100
0 2 4 6 8 10 12
Tool box (1 of 4)
Influence of modulator ions
● Different modulator ions in the core result in different release patterns.
● Release enhancing or retarding effects
Pellets containing different salts as a core and coated
with EUDRAGIT®RS as the controlled release layer
(25% w/w)
Acetate
Citrate
Succinate
Chloride
% M
eto
pro
lolSuccin
ate
rele
ased
±SD
Time in hours
15
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 29
0
20
40
60
80
100
0 2 4 6 8 10
0
20
40
60
80
100
0 2 4 6 8 10
● Release control of the modulator ion
● Fine tuning of release pattern
Tool box (2 of 4)
Influence of modulator layer
Time in hours
% T
heophyllin
e rele
ased
±SD
Time in hours
% M
eto
pro
lolSuccin
ate
rele
ased
±SD
0% EUDRAGIT® NE
20% EUDRAGIT® NE
40% EUDRAGIT® NE
0% EUDRAGIT NE
10% EUDRAGIT NE
20% EUDRAGIT NE
Pellets containing Sodium Succinate as core and
coated with different levels of modulating layer and
25% w/w EUDRAGIT® RS as the controlled release layer
Pellets containing Sodium Succinate as core and
coated with different levels of modulating layer and
25% w/w EUDRAGIT® RS as the controlled release layer
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 30
0
20
40
60
80
100
0 2 4 6 8 10 12
0
20
40
60
80
100
0 2 4 6 8 10
20% EUDRAGIT RS
25% EUDRAGIT RS
30% EUDRAGIT RS
● Increased thickness of controlled release layer decreases drug release.
● Slope of the curve can be controlled by altering the thickness of the layer.
Tool box (3 of 4)
Influence of sustained release layer
Pellets containing Sodium Succinate core and coated
with different thickness of EUDRAGIT®RS as the
controlled release layer
Time in hours
% T
heophyllin
e rele
ased +
SD
Pellets containing Sodium Citrate core and coated with
different thickness of EUDRAGIT®RS as the controlled
release layer
Time in hours
% M
eto
pro
lolSuccin
ate
rele
ased
±SD
10% EUDRAGIT® RS
15% EUDRAGIT® RS
20% EUDRAGIT® RS
25% EUDRAGIT® RS
16
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 31
Tool box (4 of 4)
Tailored release profiles can be formulated
Modulator ions
Acetate
Citrate
Succinate
Cloride
Modulator layer
EUDRAGIT® NE 30 D
Sustained release layer
EUDRAGIT® RL / RS
API
if of ionic nature
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 32
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8 9 10 11 12
0,0
1,0
2,0
3,0
4,0
5,0
0 5 10 15 20 25 30 35 40 45
Case Study Terbutaline sulphate
32.52
77.16
5.19
60.33
4.32
Bricanyl®
(7.5mg)
18.46
60.70
30.70
70.13
AUC inf (ng.h/ml)
%CV
5.32
43.00
4.09
EUDRAMODETM
(7.5mg)
4.52
69.30
C max (ng/ml)
% CV
2.61T max
Terbul
( 2*2.5mg)
% Terb
uta
line
Sulp
hate
rele
ased
±SD
Time in hours
EUDRAMODE™
Bricanyl
Terbul
Mean
Pla
sm
a T
erb
utlin
e
Concentration
±S. D. (n
g/m
l)
Time in hours
EUDRAMODETM
Bricanyl
Terbul
17
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 33
5080Rel BA
%
518.6
89.7
812.9
80.7
AUC inf (ng.h/ml)
%CV
79.6
64.1
10.8
EUDRAMODETM
32.2
69.8
C max (ng/ml)
% CV
9.1T max
Beloc-zok®
Case Study Metoprolole
0
20
40
60
80
0 5 10 15 20 25 30 35 40 45 50Mean
Pla
sm
a M
eto
pro
lolConcentration
(ng/m
L)
EUDRAMODETM
Beloc-zok®
% M
eto
pro
lolSuccin
tere
leased
0
20
40
60
80
100
120
0 2 4 6 8 10 12 14 16 18 20
EUDRAMODETM
Beloc-zok®
Time in hoursTime in hours
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 34
0
20
40
60
80
100
0 2 4 6 8 10 12
0
20
40
60
80
100
0 2 4 6 8 10 12
Storage stability
Terbutaline and Metoprolole formulations
● Assay within the limits of 95 -105% of dose with 2% RSD.
● Dissolution within the range of about ±10 % from the initial reading
in all storage conditions.
Stability of EUDRAMODETM:
Terbutaline Sulphate formulation
Time in hours
% T
erb
uta
line
Sulp
hate
rele
ased
±S.D
.
Stability of Pellets of Terbutaline Sulphate formulation
studied as per ICH conditions
Stability of EUDRAMODETM:
Metoprolol Succinate formulation
Time in hours
% M
eto
pro
lolre
leased
±S.D
.
Stability of Pellets of Metoprolol Succinate formulation
studied as per ICH conditions
Initial release
1 year stability-25 deg /60 % RH
1 year stability-30 deg /65 % RH
6 month stability-40 deg /75 % RH
Initial release
1 year stability-25 deg /60 % RH
1 year stability-30 deg /65 % RH
6 month stability-40 deg /75 % RH
18
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 35
Agenda
Matrix Formulations:
• pH-controlled
• Time-controlled
• Case study: Bupropion HCl SR tablets
Multi-layer coatings
• Drug delivery system EUDRACOL®
• Modulated drug release
Solubility enhancement:
• Melt extrusion
• Spray drying
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 36
The number of poorly soluble drugs
is increasing
Marketed drugs
25%
10%
30%
35%
BCS I BCS II BCS III BCS IV
Solubility
Perm
eability
Biopharmaceutical Classification System
IV III
II I
New Chemical Entities
5%
20%5%
70%
BCS I BCS II BCS III BCS IV
Class I: High solubility and high GI absorption
Class II: Low solubility and high GI absorption
Class III: High solubility and low GI absorption
Class IV: Low solubility and low GI absorptionFrom: Benet L. Wu C.-Y. et al 2006,
Bulletin Technique Gattefosse 99:9-16
19
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 37
Improving drug solubility
Physical methods:
• Micronization/nanosizing
• Polymorph
• Changing the crystal habit
• Complexation
• Solubilization
• Solid dispersions
Chemical methods:
• More soluble prodrugs
• Salt formation
Leuner C, Dressman J: Improving drug solubility for oral delivery using solid dispersions
Eur J Pharm Biopharm 50 (2000), 47-60
Processes:
• Melt extrusion
• Spray drying
• Coprecipitation
• Freeze drying
• Mechanical activation (co-grinding)
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 38
Case study Felodipine
Model drug: Felodipine
�1,4-Dihydropyridin calcium channel blocker
� Hypertension, angina pectoris
� neutral
� Fp: 145°C,
� Dosage: 5 to 10mg
� BCS Class II
� Aqueous solubility: 1µg/ml at 37°C
NH
Cl
Cl
O
O
O
O
NH
Cl
Cl
O
O
O
O
20
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 39
110 120120115 130 150 140 70 0
P(melt)
Ca. 12 bar
0,7 kg/h
n: 150 rpm
I: 39 %,
49%,53%
T(M2)127 °C
T(M1)146 °C
T(M3)
92 °C
1 x D 1,0
Doser 2
Powderblend
100 %
Doser 1
0 %
Balance
Conveyingdry Ice
Formulation:10%, 30%, 50%
Felodipine in
EUDRAGIT® E
Extrusion parameters
Granules were milled and sieved (<250 µm)
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 40
0
20
40
60
80
100
0 20 40 60 80 100 120
time (min)
% felo
dip
ine d
issolv
ed
Drug load optimization
USP method II (Paddle); 100 rpm, 500 ml SGFsp pH 1.2, 37°C± 0,5°C; Sample: equivalent to 10 mg felodipine
10% felodipine
30% felodipine
50% felodipine
Cryst. felodipine
Extrudates
Physical mixture
(10% felodipine)
Formation of a glassy solution leads to an inital high increase in dissolution!
21
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 41
0
20
40
60
80
100
0 30 60 90 120
crystalline Felodipine Extrudate with EUDRAGIT EPO
Extrudate with EUDRAGIT E and 5% EUDRAGIT NE
0
20
40
60
80
100
0 30 60 90 120
crystalline Felodipine Extrudate with EUDRAGIT EPO
Extrudate with EUDRAGIT E and 5% EUDRAGIT NE
Stabilization of oversaturated solution
with EUDRAGIT® NE 30 D (5%)
� water insoluble polymers can stabilize felodipine in the
oversaturated solution by adsorption effects
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 42
Melt extrusion and spray drying
show comparable results
0
20
40
60
80
100
0 15 30 45 60time (min)
% F
elo
dip
ine d
issolv
ed
Spray dried sample Extrudate felodipine
Dissolution test in pH 1.2
5 10 15 20 25 30 35
2θ (deg.)
impuls
e (re
lative)
Felodipine PM Extrudate
5 10 15 20 25 30 35
2θ (deg.)
impuls
e (re
lative)
Felodipine PM SD
22
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 43
Storage stability
� extrudates with EUDRAGIT® E, EUDRAGIT® NE and felodipine were stable over
1 year and did not show recrystallization of felodipine
� the stabilizing effect of EUDRAGIT® NE was maintained over storage time
extrudate with EUDRAGIT E, EUDRAGIT NE and felodipine
5 10 15 20 25 30 35 40
Position (2 Theta)
impuls
e (re
lativ)
1 year, 25°C/60%
1 year, 40°C/75%
6 months, 25°C/60%
40°C/75%, 6 months
freshly prepared
felodipine
Dissolution in SGFsp pH 1.2
0
20
40
60
80
100
0 30 60 90 120
time (min)
dis
solu
tion (%
)
6 months, 40°C/75% freshly prepared 1 month, 40°C/75%6 months, 25°C/60% 1 year, 25°C/60% 1 year, 40°C/75%1 month, 25°C/60%
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 44
In-vivo study in dogs
Dissolution of extrudates in SGFsp pH 1.2
0
20
40
60
80
100
0 30 60 90 120
time (min)
% d
issolv
ed
crystalline Felodipine Extrudate with EUDRAGIT EPO
Extrudate with EUDRAGIT E and EUDRAGIT NE Extrudate with acid
Dissolution of extrudates in SGFsp pH 1.2
0
20
40
60
80
100
0 30 60 90 120
time (min)
% d
issolv
ed
crystalline Felodipine Extrudate with EUDRAGIT EPO
Extrudate with EUDRAGIT E and EUDRAGIT NE Extrudate with acid
27079 (± 1704) 8210 (± 2333) 1,9 (± 1,5)D
22612 (± 8230) 10090 (± 6130) 1,5 (± 0,86)C
n.d.
9967 (±5830)
Cmax (ng/l)
25529 (±1575) 1,5 (± 1,06)B
n.d.
tmax (h)
n.d.A
AUC (ng/l/h)Form.
Mean plasma concentrations of felodipine
0
2000
4000
6000
8000
10000
0 1 2 3 4 5 6 7 8 9 10 11 12
Time (h)
Concentration (ng/l)
Formulation C: extrudate w ith EUDRAGIT E and EUDRAGIT NEFormulation B: extrudate w ith EUDRAGIT EFomrulation D: extrudate w ith acidFormulation A: physical mixture w ith EUDRAGIT E
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Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona
Summary
Leveraging their functionalities and characteristics EUDRAGIT® polymers
can be used for advanced formulations increasing therapeutic benefits.
EUDRAGIT® polymers behave as effective SR matrix formers with excellent
binding properties. Polymer quantities of 6-20% are sufficient to generate
strong retardation which in particular enables matrix formulations for highly
soluble and highly dosed actives.
By flexible double coating drug delivery systems individually designed
release characteristics can be achieved. EUDRACOL® provides colon
targeting with sustained drug release along the colonic transit.
Solid solutions based on EUDRAGIT® E enhance drug solubility with
advantageous storage stability showing increased bioavailability.
Pharma Polymers | Brigitte Skalsky 2010-12-02 Barcelona Page | 46
EVONIK Röhm GmbH
Pharma Polymers
www.pharma-polymers.com
phone: +49 (0)6151 18 4389
e-mail: [email protected]