Kollicoat Smartseal 30 D Short

8/11/2019 Kollicoat Smartseal 30 D Short

1/39

The first aqueous polymer dispersion for

taste masking & moisture protection

Kollicoat Smartseal 30 DActive Protection.

Pharma Ingredients & Services

Customer presentation December 2010


2/39

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


3/39



Content


Application data



Summary

Introduction


4/39



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.


5/39


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


Formulation needs taste masking


6/39October 2010 Kollicoat Smartseal 30 D - Technical presentation 6


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




Content

Introduction

Application data



Summary





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.




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.




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.




Solubility

0

1

23

4

5

6

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.




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

Waterc

ontent[%]

The complete insensitivity to moisture determines the effectivebarrier function.


13/39




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




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.




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.




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.




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.




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




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




Content

Introduction



Summary


Application data



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


23/39



Application data

Sorbitol tablets (moisture protection)

Acetaminophen crystals

Caffeine pellets

Theophylline granules

Caffeine tablets (taste masking)

Process parameter charts

Quinine hydrochloride tablets (taste masking)


24/39



Application data



Caffeine pellets






25/39



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


26/39



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


27/39



Caffeine tablets: Dissolution at pH 6.8

0

20

40

60

80

100

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.


28/39




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]

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


29/39




0

20

40

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.


30/39



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)

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.


31/39



Application data



Caffeine pellets






32/39




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


33/39


34/39


25 75 125 175 225 275

15

20

25

30

35

40

45

50

PROCESS TIME [mi nut es]

PRODUCTTEMPERATURE[C]


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


35/39


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


surface acceptable


best results in surface quality


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


36/39



Content

Introduction

Application data


Summary




37/39




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.


38/39



Content

Introduction

Application data




Summary


39/39


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

Documents

Transcript of Kollicoat Smartseal 30 D Short