Functionalized Calcium Carbonate (FCC) · Functionalized Calcium Carbonate (FCC) FCC: Newly developed structured minerals as multifunctional excipients This document contains proprietary

ExcipientFest Americas, San Juan, PRApril 29th 2015

Dr. Carolina Diaz Quijano_ [email protected]

Functionalized Calcium Carbonate (FCC)FCC: Newly developed structured minerals as multifunctional excipients

This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.

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Omya

• Founded in 1884 in Switzerland, Omya has a global presence extending to more than 180 locations in over 50 countries with 8,000 employees.

• Omya is a leading global producer of minerals and a worldwide distributor of specialty additives.

• Omya has been present in the life sciences market for decades (food, pharmaceuticals, cosmetics, environmental products, feed and agriculture).

June 5, 2015


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Carpet cleaners

Omya FPC (Food, Pharma, Cosmetics)

June 5, 2015

Bulking agent

Gelling agent

pH buffer

Extrusion aid

Facial cream

Body lotion Body/ facial scrub

Color cosmetics

Soap bars

Hard surface cleaners

Laundry bars

White pigmentCarrier

Anti-caking agent

Toothpaste


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Omya in the Pharma market

• Active ingredient in antacids

• Natural source of calcium in osteoporosis treatment and mineral supplements

• Omya has been active in Pharma market for over 10 years

• To serve this market, two plants are available• Arizona US• Orgon FR

June 5, 2015


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Omyapure 35 OG

June 5, 2015

2μm

Omyapure 35 OG

Omya became the firstproducer of natural calcium carbonate to achieve the certificate of suitability (CEP/CoS) in accordance with the European Pharmacopoeia as an active pharmaceutical ingredient (API) by the European Directorate of the Quality of Medicines (EDQM)


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Functionalized Calcium Carbonate (FCC)

June 5, 2015

2μm

Omyapure 35 OG FCC

2μm

• Co-processed excipient• Recrystallization process• Monographed starting material• Final product mixture of monographed minerals

• Calcium carbonate• Hydroxylapatite


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• Lamellar structure• High porosity• High specific surface area

Functionalized Calcium Carbonate (FCC)

June 5, 2015

FCC

2μm


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• University of Basel, Switzerland, Department of Pharmaceutical Science, Division of Pharmaceutical Technology.

Case studies FCC as an excipient

June 5, 2015

• 3 PhD students: Dr. Tanja StirnimannDaniel PreisigVeronika Eberle


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• Drug loading onto FCC

• Compaction of FCC

• FCC in orally dispersible tablets (ODTs)


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Drug loading onto FCC and release kineticsPreisig et al. Eur J Pharm Biopharm (2014) 87:548-558

FCC + Drug dissolved in solvent

FCC loaded with drug

Solvent evaporation

2 μm 2 μm

• The study proved the feasibility of the method to load porous particles like FCC


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• 21 different drugs were tested

• 14 successfully loaded up to 25%

• 10 successfully loaded up to 40%

• Nifedipine (NP), Ibuprofen (IBU) and Losartan Potassium (LK) were further investigated

Drug loading onto FCC and release kinetics

100 μm 10 μm 5 μm


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• Amorphous drug (DSC)

Drug loading onto FCC and release kineticsPreisig et al. Eur J Pharm Biopharm (2014) 87:548-558

Preisig et al. Eur J Pharm Biopharm (2014) 87:548-558

• Dissolution rate (USP2)

��

��

� ��

• NP 8.9%• IBU 6.7%• LK 100%


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Flowability enhancementStirnimann et al. Int J Pharm (2014) 466:266-275

• High-shear granulation• 5% (w/w) HPMC E5PLV as a

liquid binder solution• Impeller speed 150 rpm• Chopper speed 1500 rpm

• Roller compaction• Roll pressure 20 bars, roll

gap 1 mm, roll speed 4rpm• FCC direct compressible• Roller compaction preserves

the unique structure of FCC


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Compaction of FCCStirnimann et al. Int J Pharm (2014) 466:266-275

• Low compressive pressure• Particles are intact• Particles with high volume of

large intraparticle pores on the surface can build type I bonds between the particles (lamellae bonds)

• High tensile strength already at low compressive pressures

• High compressive pressure• Particles break• Intraparticle pores provide

surface for new contacts• Particles with a high volume

of very small pores collapse and form type II bonds

IIII

I


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ParacetamolStirnimann et al. Int J Pharm (2014) 466:266-275

• Formulation with active pharmaceutical ingredient (API)• Tensile strenth is higher

(especially at low compressive pressures) or comparable to reference material

• Porosity decreases but is still higher compared to reference material


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Application of FCCStirnimann et al. Pharm Res (2013) 30:1915-1925

• Orally dispersible tablets (ODTs)• Fast disintegration in the mouth / in a spoon• Particularly suitable for children / elderly people

(swallowing problems)• Can be swallowed without the need of water

• Requirements for ODTs

• Combination of high porosity and high hardness• Opposite properties

• Easy manufacturing process• Direct compression (without increasing disintegration time)

• Allow• High drug load• Standard packaging


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Disintegration time – Residence timeStirnimann et al. Pharm Res (2013) 30:1915-1925

• Tensiometer based method• More sensitive than

existing methods• Mass vs Time• Water-uptake can be

measured with same device

• Allows to determine residence time

• Analysis of disintegration kinetics


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Disintegration typesStirnimann et al. Pharm Res (2013) 30:1915-1925

• Type I:• Idealized behavior

• Type II:• No disintegration

• Type III:• Nonuniform

disintegration• Type IV:

• Combination between type I and type II

• Based on the tensiometer profiles of 25 different formulations, 4 different disintegration types were distinguished

0

0.2

0.4

0.6

0.8

0 20 40 60

Mas

s (g

)

Time (s)

I: Market formulation

II: MCC + disintegrant

III: lactose monohydrate + disintegrant

IV: MCC based fillers and disintegrant


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Disintegration typesStirnimann et al. Pharm Res (2013) 30:1915-1925

• Type I:• Idealized behavior

• Type II:• No disintegration

• Type III:• Nonuniform

disintegration• Type IV:

• Combination between type I and type II

• Note:• Market formulation:

Type I, 15 N• FCC: Type I, 100 N

• Based on the tensiometer profiles of 25 different formulations, 4 different disintegration types were distinguished

0

0.05

0.1

0.15

0.2

0.25

0 5 10 15 20

Mas

s (g

)

Time (s)

I: FCC + disintegrant

I: Market formulation


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Orally dispersible granules

2 seconds


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FCC + 3% disintegrant


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Conclusion / Outlook

• FCC is a co-processed mineral excipient• FCC is a highly suitable excipient to produce tablets

with high tensile strength and high porosities• Fast disintegrating granules• ODTs

• FCC has high loading capability

• Outlook• 2 new PhD students at University of Basel

• ODT formulations with different APIs, taste masking, mouth-feel improvement

• FCC potential in different applications• Clinical trials with ODTs or Floating drug delivery

sytems (FDDS)


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Aknowledgements

• University of Basel, Department of Pharmaceutical Technology

• Professor Jörg Huwyler and Dr. Maxim Puchkow

• Dr. Tanja Stirnimann and Daniel Preisig

Documents

Functionalized Calcium Carbonate (FCC) · Functionalized Calcium Carbonate (FCC) FCC: Newly developed structured minerals as multifunctional excipients This document contains proprietary