View
662
Download
0
Category
Tags:
Preview:
DESCRIPTION
DAISO & ChromaCon: A revolutionary continuous chromatography method to purify fatty acids to achieve higher purity & yield and to reduce costs at the same time.
Citation preview
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 1
Enabling processing capabilities by significantly
reducing CAPEX and OPEX
EPA purification from fishoil using
Contichrom® (MCSGP)
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 2
Overview
Fatty acids are useful in for many applications, including in
pharmaceuticals, nutraceuticals, food supplements and chemical
intermediates
Often large volumes (multi-tons) at high purity (>80%) are required
for the applications
Classical large-scale purification techniques such as distillation
and precipiation are not capable of providing high purity fatty acids
Comparing available purification technologies, Contichrom® with
MCSGP seems to be the only available production technology
capable of producing high volume, high purity fatty acid products at
reasonable COG
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 3
Introduction: Fat, Oil
Oil (liquid at room temperature), fat (solid at room temperature):
Major -3 fatty acids:
Eicosapentaenoic acid (EPA): C20:5
Docosahexaenoic acid (DHA): C22:6
Example of an unsaturated fat triglyceride. Left part:
glycerol, right part from top to bottom: palmitic acid,
oleic acid, alpha-linolenic acid,
Source: Wikipedia
The first double bond is located at the third carbon from the methyl end of the fatty acid chain, known as
the n end. Thus, EPA acid is a polyunsaturated n−3 (omega-3) fatty acid
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 4
Case Study: Purification of ω-3 fatty acids
ω-3 fatty acids for pharmaceutical applications are
made from fish oil
Products: Omacor®/Lovaza™ (1.3 bio US$ sales)
Used as prescription medicine as a supplement to
diet for the treatment of elevated levels of
triglycerides
API of Omacor: 45% EPA-EE, 35% DHA-EE
Several companies develop biosimilar APIs
Several companies develop high purity EPA-EE
and derivatives as 2nd generation product
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 5
Case Study: MCSGP process design: 1st step
Perform analytical RP-HPLC batch chromatography
Feed purity 74%, target purity >97%
(generic fish oil feed purchased from TCI Europe N.V.)
Main impurity Docosahexaeonic acid ethyl ester (DHA-
EE)
EPA-EE DHA-EE
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 6
Case Study: MCSGP process design: 2nd step
Batch chromatography for the purification of EPA-EE, recording the
elution fraction product purity by analytical HPLC
Results: UV-signal and fraction analyses:
70%
75%
80%
85%
90%
95%
100%
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
0 5 10 15 20 25
Pu
rity HP
LC [%
]
UV
no
rm[m
AU
/mA
U]*
12,
Co
nc
[mg
/ml]
Time [min]
conc EPA-EE
UV
Purity EPA-EE
EPA-EE spec
B01on Daisogel 120-20 ODS-RPS
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 7
70%
75%
80%
85%
90%
95%
100%
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
12 13 14 15 16 17 18 19 20 21 22
Pu
rity HP
LC [%
]U
Vn
orm
[mA
U/m
AU
]*1
2, C
on
c [m
g/m
l]
Time [min]
conc EPA-EE
UV
Purity EPA-EE
EPA-EE spec
B01
Case Study: MCSGP process design: 3rd step Define sections of pure product extraction (red) and product-containing impurity
recycling (blue + green) based on prior analytical purity measurements using the
Contichrom® Software Wizard
15.8min 17.3min 19.3 min
product recycle recycle waste waste
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 8
Use Contichrom® MCSGP wizard to convert batch method into
MCSGP method by simple click on the „Write Method“ button (yellow
arrow)
Case Study: MCSGP process design: 4th step
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 9
Case Study: anatomy of one MCSGP cycle run Zoom of 1 cycle (only UV1 and tasks of column 2 shown)
W/P rec product
elution
P/S rec Cleaning and re-
equilibration
Removal of W W/P
uptake
feed P/S
uptake
Pressure
at pump 1
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 10
Results from MCSGP:
Internal UV profiles of both UV detectors shown for 5 cycles shown
Run is very consistent
Case Study: anatomy of multiple MCSGP cycles
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 11
Case Study: multiple MCSGP cycles overlay
Online evaluation of MCSGP experiment: Cycle overlay can be used to determine
if run has reached cyclic steady state and shows a consistent pattern
Example: Overlay of 5 cycles: Exact matching of product profiles in (blue) window.
Cyclic steady state: Product of constant quality and concentration is withdrawn
Product consistency shown
product
elution
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 12
Experimental verification
Performance summary:
MCSGP
(20 m
resin)
Batch
(15 m
resin)
Improvement by
MCSGP
Purity [%] >97% >97%
Yield [%] 90% 36% + 250%
Productivity (Throughput) [(g product)/(L resin)/(hr operation time)]
65 11 + 590%
Solvent Consumption [L solvent/g product]
0.8 3.2 - 75%
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 13
Purification of EPA: Scale-Up modelling Contichrom® (2 col MCSGP) Batch
Lab/prep scale
(for feasibility)
i.d. 4.5cmx15cm columns,
200kg/year
Pilot-scale
(2 t/year)
i.d. 15cmx15cm columns,
solvent: 133m3/month
i.d. 45cmx25cm column,
solvent: 530m3/month
Production-
scale
(100 t/year)
i.d. 100cmx15cm columns,
solvent: 6‘700m3/month
i.d. 317cmx25cm column,
solvent: 26‘700m3/month
Column size not
feasible in batch
© ChromaCon AG // www.chromacon.ch // EPA purification by Contichrom® 14
Conclusions from scale modelling of EPA purification
Batch chromatography not feasible on production
scale
Contichrom using MCSGP process at production
scale: 100 t/y and beyond is feasible at competitive
COG
Other multi-column production technologies (SMB
and derivatives) are inferior as they require much
larger CAPEX and OPEX
Recommended