Kollicoat Smartseal 30 D Short
Transcript of Kollicoat Smartseal 30 D Short
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The first aqueous polymer dispersion for
taste masking & moisture protection
Kollicoat Smartseal 30 DActive Protection.
Pharma Ingredients & Services
Customer presentation December 2010
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Kollicoat Smartseal 30 D
Content
Introduction
Functionalities & applications
Application data
Regulatory information & toxicological data
Packaging & storage information
Summary
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Kollicoat Smartseal 30 D
Content
Functionalities & applications
Application data
Regulatory information & toxicological data
Packaging & storage information
Summary
Introduction
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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. formulationswith 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.
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Many active ingredients exhibit a specific taste. Very often they are bitter.
Orally disintegrating tablets or sprinkles, which are easier to dose and moreconvenient 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 developpediatric medicines.
Pellet coatingTablet coatingParticle coating
Kollicoat Smartseal 30 D
Formulation needs taste masking
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Kollicoat Smartseal 30 D
Desired functionality of protective coatings
Low water permeabil ity& 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
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Kollicoat Smartseal 30 D
Content
Introduction
Application data
Regulatory information & toxicological data
Packaging & storage information
Summary
Functionalities & applications
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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) anddissolves quickly in the acidic environment of the stomach.
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Kollicoat Smartseal 30 D
Product form & composition
Kollicoat
Smartseal 30 D [methyl methacrylate -diethylaminoethyl methacrylate co- polymer
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.
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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. 57CGlass transition temperature (Tg) 57C
Water cannot act as plasticizer within the lipophilic polymer.
Consequently, the measured MFT of Kollicoat Smartseal 30 D is higherthan of other well known polymer dispersions.
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Kollicoat Smartseal 30 D
Solubility
0
1
23
4
5
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7
8
9
10
0 2 4 6 8 10 12 14
1 mol/l HCl [ml]
pH
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 dissolvesand the milky white dispersion turns into a clear solution.
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Kollicoat Smartseal 30 D
Sorption isotherm
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10
20
30
40
50
60
70
80
90
100
30 40 50 60 70 80 90 100
Rel. humidity [%]
Sorption
Desorption
Waterc
ontent[%]
The complete insensitivity to moisture determines the effectivebarrier function.
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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
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Formulation recommendations
Plasticizer
TBC, ATEC, TEC, ATBC/DS, DBS/DS
Antioxidant
BHT
PigmentsTalc
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.
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Kollicoat Smartseal 30 D
Preparation of the coating suspension
Pigments
TEC&
BHT
Plastic
iser
1
2
Kolli
coat
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 suspensionAdd 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 theplasticizer into the polymer droplets.
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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 priordilution into the dispersion.
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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 arerecommended as cleaning agents:
Coating equipment can be cleaned easily from residues of
Kollicoat
Smartseal 30 D based formulations.
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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]
Minim
umfilmformin
gtemperature
[C]
Tributyl citrate
Acetyltriethyl citrateTriethyl citrate
Acetlytributyl citrat + Docusate sodium 2%
Dibutyl sebacate + Docusate sodium 2%
recommended level
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Impact of the plasticizer concentration
mechanical properties
Plasticizer content rel. to polymer [%]
Elonga
tionatbreak[%]
The elasticity of polymer films can be increased by the addition ofplasticizers.
0
50
100
150
200
250
300
10 15 20 25
Triethyl citrate
Tributyl citrate
Acetyltriethyl citrate
casted films
recommended level
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Content
Introduction
Regulatory information & toxicological data
Packaging & storage information
Summary
Functionalities & applications
Application data
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Applications
Tablet
coating
Pellet
coating Subcoating
Taste masking
for oral
dispersiblesParticle
coatingRumen stable
DDS
Recommended coating levels:
Taste masking: 2 5 mg/cm
Moisture barrier: 5 20 mg/cm
Granulation
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Application data
Sorbitol tablets (moisture protection)
Acetaminophen crystals
Caffeine pellets
Theophylline granules
Caffeine tablets (taste masking)
Process parameter charts
Quinine hydrochloride tablets (taste masking)
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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)
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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
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Kollicoat Smartseal 30 D
Caffeine tablets: Process parameters
Machine Accela Cota, 24
Inlet air temperature 60C
Batch size 7 kg
Product temperature 30 33CSpraying 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
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Caffeine tablets: Dissolution at pH 6.8
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120
0 10 20 30 40 50 60Time [min]
Drug
release[%]
1mg/cm coating level2mg/cm coating level3mg/cm coating level4mg/cm coating level5mg/cm coating leveluncoated core
A coating level of 4 mg/cm prevents caffeine dissolution at pH 6.8 for
more than 60 minutes.
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Caffeine tablets: Dissolution at pH 1.2
Caffeine is released quickly and completely at pH 1.2.
0
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40
60
80
100
120
0 10 20 30 40 50 60
Time [min]
Drug
release[%]
1 mg/cm coating level2 mg/cm coating level3 mg/cm coating level4 mg/cm coating level
5 mg/cm coating leveluncoated cores
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Kollicoat Smartseal 30 D
Caffeine tablets: Dissolution at pH 6.8
0
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60
80
100
120
0,00 10,00 20,00 30,00 40,00 50,00 60,00
Time [min]
Drugrelease[%]
Kollicoat Smartseal 30 D based formulationBasic butylated methacrylate copolymer
based formulation
HPMC based coating system
uncoated core
A coating level of 4 mg/cm Kollicoat Smartseal 30 D can preventdissolution from caffeine tablets than other well known protective coatings.
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Kollicoat Smartseal 30 D
Caffeine tablets: Taste masking effect
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2
4
6
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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)
Numberofbittersensations*
Kollicoat Smartseal 30 DBasic butylated methacrylate
copolymer based formulationHPMC based system
Kollicoat Smartseal 30 D can effectively mask the taste of caffeine tabletsat coating levels of of 4-5 mg/cm.
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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)
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Process parameter charts
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 itsprocessabilty in varying equipment and scale.
producttemperature[C]
Process time [min] = [ ]
contentmattersolidg
ratespray
gainweightgsizebatch
min
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25 75 125 175 225 275
15
20
25
30
35
40
45
50
PROCESS TIME [mi nut es]
PRODUCTTEMPERATURE[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
Optimal film coating process;
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
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25 75 125 175 225 275
15
20
25
30
35
40
45
50
PROCESS TIME [m inu tes]
PRODUCTT
EMPERATURE[C]
Film coating impossible;
sticking of the cores
Film coating principally possible
surface not acceptable
Optimal film coating process;
surface acceptable
Optimal film coating process;
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
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Kollicoat Smartseal 30 D
Content
Introduction
Application data
Packaging & storage information
Summary
Functionalities & applications
Regulatory information & toxicological data
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Kollicoat Smartseal 30 D
Regulatory information & toxicological data
Kollicoat Smartseal 30 D is a new excipient. There are no registered drug productsyet.
The pharmacokinetics and the pre-clinical safety of Kollicoat Smartseal 30 D areadequately documented by in vitro and in vivo studies that were in line with thecurrent international guidelines, regulations and recommendations.
In the US, there will be Type IV and Type V Drug Master Files for KollicoatSmartseal 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 wewill assist our customers who are in the process of filing.
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Kollicoat Smartseal 30 D
Content
Introduction
Application data
Packaging & storage information
Regulatory information & toxicological data
Functionalities & applications
Summary
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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