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

Transcription

1 Functionalized Calcium Carbonate (FCC) FCC: Newly developed structured minerals as multifunctional excipients ExcipientFest Americas, San Juan, PR April 29 th 2015 Dr. Carolina Diaz Quijano_ 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). 2

2 Omya FPC (Food, Pharma, Cosmetics) ph buffer Facial cream Bulking agent Body lotion Body/ facial scrub Gelling agent Toothpaste Anti-caking agent Laundry bars Extrusion aid Soap bars Carrier Color cosmetics White pigment Carpet cleaners Hard surface cleaners 3 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 4

3 Omyapure 35 OG Omyapure 35 OG 2μm 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) 5 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 6

4 Functionalized Calcium Carbonate (FCC) Lamellar structure High porosity High specific surface area FCC 2μm 7 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 8

5 Case studies FCC as an excipient Drug loading onto FCC Compaction of FCC FCC in orally dispersible tablets (ODTs) 9 Case studies FCC as an excipient Drug loading onto FCC Compaction of FCC FCC in orally dispersible tablets (ODTs) 10

6 Drug loading onto FCC and release kinetics Preisig et al. Eur J Pharm Biopharm (2014) 87: FCC + Drug dissolved in solvent Solvent evaporation FCC loaded with drug 2 μm 2 μm 11 The study proved the feasibility of the method to load porous particles like FCC 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 10 μm 5μm 12

7 Drug loading onto FCC and release kinetics Preisig et al. Eur J Pharm Biopharm (2014) 87: Amorphous drug (DSC) NP 8.9% IBU 6.7% LK 100% Dissolution rate (USP2) 13 Preisig et al. Eur J Pharm Biopharm (2014) 87: Case studies FCC as an excipient Drug loading onto FCC Compaction of FCC FCC in orally dispersible tablets (ODTs) 14

8 Flowability enhancement Stirnimann et al. Int J Pharm (2014) 466: 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 15 Compaction of FCC Stirnimann et al. Int J Pharm (2014) 466: 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 II I I 16

9 Paracetamol Stirnimann et al. Int J Pharm (2014) 466: 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 Case studies FCC as an excipient Drug loading onto FCC Compaction of FCC FCC in orally dispersible tablets (ODTs) 18

10 Application of FCC Stirnimann et al. Pharm Res (2013) 30: 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) 19 Allow High drug load Standard packaging Disintegration time Residence time Stirnimann et al. Pharm Res (2013) 30: 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 20

11 Disintegration types Stirnimann et al. Pharm Res (2013) 30: Based on the tensiometer profiles of 25 different formulations, 4 different disintegration types were distinguished Type I: Idealized behavior Type II: No disintegration Type III: Nonuniform disintegration Type IV: Combination between type I and type II Mass (g) II: MCC + disintegrant IV: MCC based fillers and disintegrant I: Market formulation III: lactose monohydrate + disintegrant Time (s) 21 Disintegration types Stirnimann et al. Pharm Res (2013) 30: Based on the tensiometer profiles of 25 different formulations, 4 different disintegration types were distinguished 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 Mass (g) I: Market formulation I: FCC + disintegrant Time (s) 22

12 Orally dispersible granules 2 seconds 23 FCC + 3% disintegrant 24

13 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) 25 Aknowledgements University of Basel, Department of Pharmaceutical Technology Professor Jörg Huwyler and Dr. Maxim Puchkow Dr. Tanja Stirnimann and Daniel Preisig 26