Excipient Fest talk - IPEC

Functionalized Calcium
Carbonate (FCC)
FCC: Newly developed structured minerals as
multifunctional excipients
ExcipientFest Americas, San Juan, PR
April 29th 2015
Dr. Carolina Diaz Quijano_ [email protected]
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).
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Omya FPC (Food, Pharma, Cosmetics)
pH buffer
Facial cream
Bulking agent
Body/ facial scrub
Body lotion
Toothpaste
Gelling agent
Laundry bars
Anti-caking agent
Soap bars
Extrusion aid
Carrier
White pigment
Color cosmetics
Carpet cleaners
Hard surface cleaners
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
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
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Omyapure 35 OG
Omyapure 35 OG
2μm
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Omya became the first
producer 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)
June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Functionalized Calcium Carbonate (FCC)
Omyapure 35 OG
FCC
2μm
2μm
• Co-processed excipient
• Recrystallization process
• Monographed starting material
• Final product mixture of monographed minerals
• Calcium carbonate
• Hydroxylapatite
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Functionalized Calcium Carbonate (FCC)
• Lamellar structure
• High porosity
• High specific surface area
FCC
2μm
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Case studies FCC as an excipient
• University of Basel, Switzerland, Department of
Pharmaceutical Science, Division of Pharmaceutical
Technology.
• 3 PhD students: Dr. Tanja Stirnimann
Daniel Preisig
Veronika Eberle
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June 5, 2015
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Drug loading onto FCC and release kinetics
Preisig et al. Eur J Pharm Biopharm (2014) 87:548-558
Solvent evaporation
FCC loaded
with drug
FCC + Drug dissolved
in solvent
2 μm
2 μm
• The study proved the feasibility of the method to
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load porous particles like FCC
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Drug loading onto FCC and release kinetics
• 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
100 μm
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
10 μm
5 μm
Drug loading onto FCC and release kinetics
Preisig et al. Eur J Pharm Biopharm (2014) 87:548-558
• Amorphous drug (DSC)
• NP 8.9%
• IBU 6.7%
• LK 100%
ܺܽ Ψ ൌ ͳͲͲ െ
ȟ‫݀ܽ݋݈ܪ‬
‫ͲͲͳ כ‬
ȟ‫ݔ݅݉ܪ‬
• Dissolution rate (USP2)
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Preisig et al.
Eur J Pharm Biopharm (2014) 87:548-558
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
14
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Flowability enhancement
Stirnimann 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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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Compaction of FCC
Stirnimann 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
I
I
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
II
I
Paracetamol
Stirnimann 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
17
This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Case studies FCC as an excipient
• Drug loading onto FCC
• Compaction of FCC
• FCC in orally dispersible tablets (ODTs)
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Application of FCC
Stirnimann 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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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Disintegration time – Residence time
Stirnimann 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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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Disintegration types
Stirnimann et al. Pharm Res (2013) 30:1915-1925
• Based on the tensiometer profiles of 25 different
formulations, 4 different disintegration types were
distinguished
0.8
• Type I:
•
II: MCC + disintegrant
Idealized behavior
• Type II:
No disintegration
• Type III:
•
Nonuniform
disintegration
0.6
Mass (g)
•
I: Market formulation
• Type IV:
•
IV: MCC based fillers and disintegrant
0.4
0.2
Combination between
type I and type II
III: lactose monohydrate + disintegrant
0
0
20
40
60
Time (s)
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Disintegration types
Stirnimann et al. Pharm Res (2013) 30:1915-1925
• Based on the tensiometer profiles of 25 different
formulations, 4 different disintegration types were
distinguished
• Type I:
•
0.25
Idealized behavior
• Type II:
• Type III:
•
0.2
I: Market formulation
No disintegration
Nonuniform
disintegration
Mass (g)
•
0.15
0.1
• Type IV:
•
Combination between
type I and type II
• Note:
I: FCC + disintegrant
0.05
0
Market formulation:
Type I, 15 N
• FCC: Type I, 100 N
•
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
0
5
10
Time (s)
15
20
Orally dispersible granules
2 seconds
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
FCC + 3% disintegrant
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
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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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.
Aknowledgements
• University of Basel, Department of Pharmaceutical
Technology
• Professor Jörg Huwyler and Dr. Maxim Puchkow
• Dr. Tanja Stirnimann and Daniel Preisig
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This document contains proprietary information which shall not be
used and disclosed without Omya explicit written authorization.