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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.
2
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
3
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
4
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
5
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)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
6
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
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• Lamellar structure• High porosity• High specific surface area
Functionalized Calcium Carbonate (FCC)
June 5, 2015
FCC
2μm
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
8
• 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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
9
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
10
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
11
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
12
• 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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
13
• 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)
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• NP 8.9%• IBU 6.7%• LK 100%
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
14
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
15
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
16
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
17
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
18
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
19
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
20
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
21
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
22
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
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
23
Orally dispersible granules
2 seconds
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
24
FCC + 3% disintegrant
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
25
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)
This document contains proprietary information which shall not beused and disclosed without Omya explicit written authorization.
26
Aknowledgements
• University of Basel, Department of Pharmaceutical Technology
• Professor Jörg Huwyler and Dr. Maxim Puchkow
• Dr. Tanja Stirnimann and Daniel Preisig