SOLUTIONS FOR

TABLET FILM COATING

Pharma GBU
Customer Technical Services

NOV 2018 (SEA) - Not intended for reproduction or distribution 1

 AGENDA

1 2
Intro : LYCOAT® & ReadiLYCOAT®

Existing coating solutions pros & cons

3 LYCOAT® / ReadiLYCOAT® : benefits
4 Conclusion

2 NOV 2018 (SEA) - Not intended for reproduction or distribution 2

 INTRODUCTION
LYCOAT® & ReadiLYCOAT®

A pregelatinized modified pea starch

LYCOAT®
designed for film coating application.

A range of ready mix coating system

in a dry powder form based on LYCOAT® :
ReadiLYCOAT® : improves the appearance
ReadiLYCOAT®
of your tablets, capsules & granules
ReadiLYCOAT® MS : provides
protection against moisture.

3 NOV 2018 (SEA) - Not intended for reproduction or distribution 3

 AGENDA

1 Intro : LYCOAT® & ReadiLYCOAT®

2 3
Existing coating solutions pros
& cons

LYCOAT® / ReadiLYCOAT® : benefits

4 Conclusion

4 NOV 2018 (SEA) - Not intended for reproduction or distribution 4

 ANALYSIS OF COATED TABLET FORMULATIONS
1. Ranitidine tablets
Inactive ingredients : FD&C blue #1 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, natural and artificial mint flavor,
sucralose, titanium dioxide, triacetin
Ist generation of coating systems
2. Pseudoephedrine hydrochloride tablet, film coated
Inactive ingredients : carnauba wax, dibasic calcium phosphate, FD&C red no. 40 aluminum lake, hypromellose, magnesium stearate, microcrystalline
cellulose, polyethylene glycol, polysorbate 80, silicon dioxide, titanium dioxide
Ist generation of coating systems
3. Acetaminophen, aspirin,
wax, crospovidone, FD&C blue #1 aluminum lake, hypromellose, microcrystalline cellulose, povidone, pregelatinized starch, propylene glycol, saccaffeine
tablet, film coated .
Inactive ingredients : carnauba charin sodium, stearic acid, titanium dioxide
Ist generation of coating systems
4. Fexofenadine hydrochloride tablet, film coated.
Inactive ingredients : Colloidal silicon dioxide, croscarmellose sodium, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, lactose
monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, titanium dioxide
2nd generation of coating systems diluted with lactose
5. Ibuprofen tablet, film coated
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol,
polyvinyl alcohol, stearic acid, talc, titanium dioxide.
2nd generation of coating system PVA based
CONCLUSION :
5 different coated tablets – 5 different coating formulations (combination of polymer plasticizer)
3 different types of coating systems (HPMC, HPMC + lactose, PVA)
1 ReadiLYCOAT ® formulation (combination polymer/plasticizer) should be sufficient.
Color is specific and is excluded from the factor of differentiation between the formulas
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WHY 5 DIFFERENT FORMULATIONS FOR 5 TABLETS?

 1st generation coating systems (no filler)

Benefit Proven product performance

Low solid content of coating solutions

1
resulting in long coating process.
Drawbacks

Stability issues due to formic acid

and formaldhehyde (impurities from PEG
2 – require a plasticizer change
e.g. triacetin)

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 PEG (BY-PRODUCTS) – STABILITY ISSUES

Irbesartan reaction with

formaldehyde (BMS/Novatia, 2008) The degradation product was
detected during the long term
stability studies of the coated tablets
at 50°C during 9 weeks.
Degradation occurred in tablets
coated with a ready-to-use PVA Degradation was confirmed after
solution containing PEG as a the testing of binary coating
plasticizer. formulation and irbesartan mixes
after 8 days at 65°C.

A., Ray, Kenneth L. IdentifiWang, George, Fiske, John D., Jennings, Scott P., Tomasella, Frank P., Palaniswamy Venkatapuram cation and Control of
a. Pharmaceutical development and technology, volume 13 no 5, pages 393-397. Degradation Product in AvaproTM Film-Coated Tablet: Low Dose
Formulation. 2008

LYCOAT® and ReadiLYCOAT®

formulation are PEG free.

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WHY 5 DIFFERENT FORMULATIONS FOR 5 TABLETS?

 2nd generation coating systems (HPMC diluted with lactose)

Benefits vs Decrease viscosity (less polymer), claimed

1 generation to improve adhesion.
st

1 Weaker film strenght (due to

decrease of polymer/film former content)
Drawbacks

Stability issues with amine function

2
(Maillard reaction)

Stability issues due to formic acid and

3 formaldhehyde (impurities from PEG –
require a plasticizer change e.g triacetin)

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 FILLER – FILM RIGIDITY

Film made form formulation ReadiLYCOAT ® : LYCOAT ® ReadiLYCOAT® combines

A: HPMC, lactose(filler), PEG
8000, Talc
No film integrity, highly
brittle (will lead to edge
chipping )
glycerol, stearic acid Soft low viscosity with excellent
film film forming properties and
strength without fillers.

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 FILLER – “SUGARS” – STABILITY ISSUES

 Maillard reaction

 Fillers :
 Maltodextrin
 Lactose
 Polydextrose

ReadiLYCOAT® does not

Contain reducing sugar

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 WHY 5 DIFFERENT FORMULATIONS FOR 5 TABLETS?

 2nd generation coating systems (PVA)

Benefit
vs 1st Low viscosity (lower polymer viscosity).
generation
Benefit
vs 2nd Suitable with amine function
generation

Tackiness (due to PVA) requiring high

1 tablet bed temperature
Drawbacks

Stability issues with acidic ingredients

2 (due to PVA)

Stability issues due to formic acid and

3 Formaldhehyde (impurities from PEG-
Large quantities to counter PVA tackiness

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 PVA STABILITY ISSUES

 Investigation into Stability of Poly(Vinyl Alcohol)-Based Opadry® II Films.

Drug Product Science and Technology, Bristol-Myers Squibb Company, 1 Squibb Drive, New
Brunswick, New Jersey, 08903, USA, otilia.koo@bms.com.
Abstract
Poly(vinyl alcohol) (PVA)-based formulations are used for pharmaceutical tablet coating with numerous advantages. Our objective is to
study the stability of PVA-based coating films in the presence of acidic additives, alkaline additives, and various common impurities typically
found in tablet formulations. Opadry® II 85F was used as the model PVA-based coating formulation. The additives and impurities were
incorporated into the polymer suspension prior to film casting. Control and test films were analyzed before and after exposure to 40°C/75%
relative humidity. Tests included film disintegration, size-exclusion chromatography, thermal analysis, and microscopy.

Under stressed conditions,

Acidic additives (hydrochloric acid (HCl) and ammonium bisulfate (NH(4)HSO(4)) negatively
impacted Opadry® II 85F film disintegration
while NaOH, formaldehyde, and peroxide did not. Absence of PVA species from the disintegration
media corresponded to an increase in crystallinity of PVA for reacted films containing HCl. Films
with NH(4)HSO(4) exhibited slower rate of reactivity and less elevation in melting temperature with
no clear change in melting enthalpy.
Acidic additives posed greater risk of compromise in disintegration of PVA-based coatings
than alkaline or common impurities.
The mechanism of acid-induced reactivity due to the presence of acidic salts (HCl vs.
NH4HSO4) may be different.

12 NOV 2018 (SEA) - Not intended for reproduction or distribution 12

 AGENDA

1 Intro : LYCOAT® & ReadiLYCOAT®

2 Existing coating solutions pros & cons

3 4
LYCOAT® / ReadiLYCOAT®:benefits

Conclusion

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 ReadiLYCOAT® - LOW VISCOSITY / QUICK COATING

1600

1400

1200 PVA
Viscosity (mPa.s)

1000
HPMC 6-cps Lycoat® RS 720
800

600

400 Lycoat® RS780

200

0 Dry matter (per

5 10 15 20 25 cent)

• Optimum viscosity: 150 to 300 mPa.s

• Upper viscosity limit for uniform spraying: 500 mPa.s

LYCOAT® RS 780 < LYCOAT® RS 720 < PVA < HPMC 6-cps

ReadiLYCOAT® provides low viscosity/high solid content solution for a quick coating without
the use of fillers ensuring perfect stability and film strength
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 LOW VISCOSITY – SUSPENDING EFFECT

Cartamine (yellow color from LYCOAT® has better suspending

safflower) et gardenia blue (from the properties versus competitor products
gardenia fruit) after 24 h (ex: adapted to nanosuspension coating)

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 LYCOAT® - EASE OF DISPERSION
Quick Suspension Preparation

Complete hydration

Due to
HPMC
lumps

300 RPM 600 RPM

Hydration times:
LYCOAT® RS 780 < PVA < HPMC 6-cps

LYCOAT® RS 780 hydrates more quickly than PVA and than HPMC
speeding up coating suspension preparation

16 NOV 2018 (SEA) - Not intended for reproduction or distribution 16

 LYCOAT® - EASE OF DISPERSION
Quick Suspension Preparation

LYCOAT®
is a pregelatinized
hydroxypropyl pea starch
that has superior
wettability and
dissolution compared to
PVA and HPMC allowing
you to prepare your
coating suspension in a
very short period of
time (10-20 minutes)

17 NOV 2018 (SEA) - Not intended for reproduction or distribution 17

 ReadiLYCOAT® – LOW TABLET BED T°

Ready-made
PVA based HPMC based LYCOAT® based
Batch size 120 120-160 105
Solids 20 per cent 15 per cent 20 per cent
Weight gain 4 per cent 3 per cent 3 per cent
Number of nozzles 3 3-4 3
Atomising air pressure 3.5 bars 2.5 bars 2.8 bars
Fan air pressure 2.5
Air flow rate 2900 2300-3060
Pan diameter 48’’ 48’’ 48’’
Pan speed 8 8 5-10
Bed temperature 45-48 42-45 32-36
Solution flow rate 140 260-420 250
Coating time 190 57-123 63

LYCOAT® and ReadiLYCOAT® can be coated at 32 to 36°C tablet bed temperature and for
specific needs at ambiant temperature
Without causing defects (no sticking)

Preserving tablet stability

Limiting energy consumption to warm inlet airflow after dehydration

18 NOV 2018 (SEA) - Not intended for reproduction or distribution 18

 ReadiLYCOAT® - HEAT SENSITIVE FORMULATIONS

Tablet: sorbitol + Magnesium stearate

20 per cent solids solution
Coating conditions: Cold coating Hot coating
Rotation speed (RPM) 8.5 8.5
Inlet air temperature (°C) 19-20 45-47
Bed temperature (°C) 19-20 37-38
Atomising air pressure (bar) 1 1 Low High
temp. temp.
Fan air pressure (bar) 1 1
Core quantity (Kg) 5 5
Solution flow rate (g/min/kg) 0.9 0.9
Quantity of solution sprayed 750 750
(ml)

Low temperature minimize tablet component solubilization

19 NOV 2018 (SEA) - Not intended for reproduction or distribution 19

 ReadiLYCOAT® – QUICK CLEANING

Viscosity (Pa.s-1) 0.25

LYCOAT® RS 780
0.20
HPMC 6-cps
0.15
0.10
0.05
0 Temperature (°C)
20 40 60 80
• HPMC
Almost insoluble in hot water (gelation phenomenon)
Consequence : temperature of cleaning water (limited to 40°C)
Result : longer cleaning time and use of more detergents
• LYCOAT®
Soluble in cold and hot water. Its viscosity decrease with temperature
allowing a quick cleaning limiting the use of detergents.
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 ReadiLYCOAT® – SUPERIOR INERTNESS

Non-coated
tablet
LYCOAT®
HPMC

• Polyphenol dissolution is delayed and incomplete for HPMC-coated tablets.

• For LYCOAT®-coated tablets, dissolution is identical to that of tablet cores both
qualitatively (kinetics) and quantitatively.

21 NOV 2018 (SEA) - Not intended for reproduction or distribution 21

 ReadiLYCOAT® – SUPERIOR INERTNESS

• Compatibility study:
LYCOAT® is inert.
Interaction occurs between
cellulose derivatives (HPMC
and HPC) and polyphenols.

• Although LYCOAT®
(hydroxypropyl starch),
HPMC & HPC (hydroxypropyl
cellulose) are chemically
close, they react very
differently.

22 NOV 2018 (SEA) - Not intended for reproduction or distribution 22

 ReadiLYCOAT®– NATURAL COLORS

23 NOV 2018 (SEA) - Not intended for reproduction or distribution 23

 ReadiLYCOAT® – NATURAL COLORS

GREEN COATED TABLET

Control T+1 ReadiLYCOAT® Control ReadiLYCOAT®

W trial T+1 W T+2 W T+2 W

∆E 4.69 0.82 7.62 1.12

YELLOW COATED TABLET

Control T+1 ReadiLYCOAT® Control ReadiLYCOAT®

W trial T+1 W T+2 W T+2 W
∆E 2.34 1.67 5.21 2.61

ReadiLYCOAT ® formulation increase the intensity of natural

colors and increase their stability

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 ReadiLYCOAT® – NATURAL COLORS

HPMC (dark / light) 3 days LYCOAT® (dark / light) 3 days

 Exberry® Shade Cherry Red, GNT

 Concentration 14,68

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 REGULATORY / REGISTRATION

• Europe: E 1440 (European directive on

food additives
• U.S. : Food Chemical Codex V,
modified starch
• Japan : Food Additive

Food Status

• Europe: monograph (Eur Ph addendum

7.8 December 2012
• U.S. : monograph (USP 35-NF 30 2S
June 2012

Pharmaceutical Status
• DMF type IV n°23917
• Hydroxypropyl starch used in medicine
approved by FDA
• Use: in the shell of soft capsule formulation
free of gelatin
• Brand name: Rayaldee®, Company name:
Opko Health Inc.
Registration

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 MARKET FEEDBACK

Use in pellet (sub coating of ER or for IR) and

tablet coating

Immediate release performance (fastest dissolution time)

Stability / inertness :
Low temperature – heat sensitive materials
Chemical stability – less impurities (peroxides…)
vs HPMC, PVA, PEG….

27 NOV 2018 (SEA) - Not intended for reproduction or distribution 27

 AGENDA

1 Intro : LYCOAT® & ReadiLYCOAT®

2 Existing coating solutions pros & cons
3 LYCOAT® / ReadiLYCOAT® : benefits

4 Conclusion

28 NOV 2018 (SEA) - Not intended for reproduction or distribution 28

 CONCLUSION

LYCOAT® / ReadiLYCOAT® meet all your expectations :

29 NOV 2018 (SEA) - Not intended for reproduction or distribution 29

 THANK YOU

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