This presentation gives a definition about clean labelling in general, critical excipients discussed by the industry and TiO2 free formulations.

1. Clean labelling for
solid oral dosage forms

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Clean Label in general
- Clean label is a consumer driven movement,
demanding a return to real food and transparency
through authenticity.
- Nutraceuticals should contain natural, familiar, simple ingredients that are easy to recognize,
understand, and pronounce.
- Industry has to look for new excipients & ingredients
- No artificial ingredients or synthetic chemicals
- Consumer-friendly labelling
- Remember: Consumers & customers paying attention to the list of ingredients &
are good informed

3. Clean Label in general
There are a few accepted challenges faced by
the brand owner and the contract manufacturing
organization (CMO) when developing such products:
- Find natural, non-GMO ingredients
- Source organic ingredients when available
- Keep products allergen/gluten-free
- Correctly manufacture products without traditional manufacturing aids
(excipients/non-active ingredients)
- Minimize use of additives and fillers
- Changes to regulatory requirements lead to formulation adjustments
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4. Critical Excipients currently discussed by the
industry (e.g. Flow agent / Lubricant / Binder / Filler / Pigment)
Synthetic colors yes/no
Iron oxides yes/no
Silicon dioxide yes/no
Magnesium stearate yes/no
Titanium dioxide yes/no
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Titanium dioxide (TiO2) – a critical excipient ?
• E171 - one of the most important food addtives in nutraceuticals,
widely used as a whitening agent (e.g. in tablets or tablet film coating)
• Titanium dioxide –
the white pigment with highest
refractive index and brightness
• A excipient with unique properties –
even a low content of titanium dioxide
provides a signifcant influence to
nutraceutical products
... but why is titanium dioxide considered as critical ?

6. Titanium dioxide (TiO2) – a critical excipient ?
• Several current studies describe a potential risk of TiO2
nanoparticles (NP) to the human respiratory system.
• Consumers & customers paying attention to the list
of ingredients and are good informed !
• A clearly perceived market trend in Nutraceuticals –
a more natural & shortened ingredient list !
• Industry has to look for new alternative excipients & ingredients
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7. Challenges of TiO2 free film coatings
... film coating users & manufacturers have to face several challenges by developing
TiO2 free film coating formulations
• Alternative raw materials require a higher content in a formulation compared to TiO2 – there are
only limited possibilities due to necessary amounts of
functional excipients!
• Ensuring of comparable film-coating functions and film-coating properties like TiO2 containing
formulations
• Decisive film-coating properties for TiO2 free film coatings: brightness & opacity
• Ensuring a similar preparation and application of TiO2 free film coatings
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8. Alternative raw materials for TiO2 free film coatings
... there are several possible replacements for titanium dioxide e.g.
Carbonates
Phosphates
Starches
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9. Evaluation of possible
replacements for titanium dioxide
in film coating systems
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10. Material and Methods
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12 investigated formulations containing 5 different
replacements for TiO2 with different particle sizes in
a “standard film-coating formulation”
Core formulation of different vitamins, widely used in nutritionals
Standardized film-coating process in a fully perforated drum
Comparison of different weight gain levels
Investigated film-coating properties were:
- opacity and brightness
- film flexibility, strength & surface
- viscosity
uncoated cores

11. Used devices
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Equipment used for blending and film-coating process
Lab Coater
Bosch Solidlab I
Propeller stirrer for
preparing suspension
Blending/mixing of
film coating ingredients

12. Used devices
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Equipment used for characeterizing film-coating properties
Colourimeter Texture Analyzer Viscosometer

13. Results and Discussion
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Comparison of different film-coating formulations at 3% of weight gain
AquaPolish® formula I AquaPolish® formula with Ti02
∆E 10,13
Opacity - +
Brightness - +
Film flexibility + +
Film strength + +
Film surface o +
Viscosity 475 mPa*s 513 mPa*s

14. Results and Discussion
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Comparison of different film-coating formulations at 3% of weight gain
∆E 6,68
Opacity o +
Brightness o +
Film flexibility + +
Film strength + +
Film surface + +
Viscosity 466 mPa*s 513 mPa*s
AquaPolish® formula with Ti02AquaPolish® formula II

15. Results and Discussion
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Comparison of different film-coating formulations at 3% of weight gain
∆E 3,8
Opacity o +
Brightness o +
Film flexibility + +
Film strength + +
Film surface o +
Viscosity 540 mPa*s 513 mPa*s
AquaPolish® formula with Ti02AquaPolish® formula III

16. Results and Discussion
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Comparison of different film coating formulations at 5% of weight gain
∆E 1,2
Opacity + +
Brightness o +
Film flexibility + +
Film strength + +
Film surface + +
Viscosity 526 mPa*s 513 mPa*s
AquaPolish® formula with Ti02AquaPolish® formula IV

17. Conclusion
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• AquaPolish® formula I bad opacity & brightness
• AquaPolish® formula II bad opacity and brightness, good film-surface
• AquaPolish® formula III good opacity & brightness, acceptable film-surface
• AquaPolish® formula IV good opacity, brightness & film surface
 using a mixture out of different replacements for combining properties
 using a higher weight gain level for increasing the properties of the replacements

18. Conclusion
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There are suitable replacements for titanium dioxide in film coatings
The mixture of different replacements can combine several raw-material properties
for getting a comparable TiO2 free film coating
TiO2 free film coatings can be processed and applicated comparable
like typical film coatings:
 amount of weight gain
 process time
 product price

19. Conclusion
... as an answer to the consumers demand:
- TiO2 free formulation (white or coloured) are available
- formulated with alternative raw materials for whitening
- comparable opacity & brightness can be achieved
- Manufacturers can meet market demand
(products with or without TiO2)
with TiO2
TiO2 free
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20. Contact Europe Contact USA Contact Russia
BIOGRUND GmbH BIOGRUND International AG BIOGRUND US, Inc. OOO BIOGRUND
T +49 6126-952 63-0 T +41 (0) 41-747 14-50 T +1 (703) 665-2147 T +7 495 116 0368
info@biogrund.com team@biogrund.com contact@biogrund.com info@biogrund.ru
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Members:
BIOGRUND, BOSCH Packaging Technology,
LONZA Inc., NATOLI Engineering Company,
RIBUS Inc.