an r&d service performed for a mid-sized pharmaceutical ... · the api involved herein is in...
TRANSCRIPT
CASE STUDY
An R&D service performed for a mid-sized pharmaceutical company
Two-Steps Purification with E-PAK® Cartridges Following a Direct Pd-Catalyzed BorylationUnpublished raw data
This project was initiated by a SiliCycle customer and fine-tuned by SiliCycle thereafter
CHALLENGE & PROJECT SCOPE
Optimization of a Palladium purification protocol, following a borylation reaction, using E-PAK® cartridges; comparison with traditional purification techniques.
HIGHLIGHTED BENEFITS & ADVANTAGES
In the standard process, five dedicated operations are required to reduce Pd levels to less than 20 ppm:• 1st filtration on activated carbon followed by washings• 2nd washing of the obtained organic phase with conc. HCl to achieve an effective phase separation• 2nd filtration on activated carbon followed by washings• Treatment with SiliaMetS Thiol for 6 h• 3th filtration, followed by evaporation• Recrystallisation
All of the above was successively replaced by treatments on E-PAK carbon (C-947, 2-3 passes) and E-PAK SiliaMetS (DMT, 7-8 passes) cartridges at room temperature.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology 1
PROJECT
This work was sponsored by a mid-sized pharmaceutical company that is a SiliCycle customer since 2014. The API involved herein is in Phase III trials.
In this project, after evaluating various & more traditional purification means, they opted for SiliCycle’s SiliaMetS Metal Scavengers for the efficient removal of Palladium which was contaminating a synthetic intermediate following a direct Pd-catalyzed borylation reaction.
SiliCycle was able to successfully optimize the entire purification protocol through its new integrated solution: E-PAK® radial-flow cartridges, a product specifically developed for pharmaceutical purifications from R&D scale to full production. Advantages of this technology include full recovery of API, marginal leaching, solvent & extended pH range compatibility, straightforward scalability, environment friendly, sounds economics. The details of this optimization are described below.
As part of a large scale manufacturing process, the purification of a direct Pd-catalyzed borylation step was initially performed via two successive treatments: a two-pass filtration through activated carbon (using twice the same carbon filtration cartridge), followed by a Palladium scavenging step with SiliaMetS Thiol.
I
OB
O** O **B
O
+
1. Pd(OAc)2 (0.029 equiv.) Ph3P (0.040 equiv.)
Cs2CO3 (1.5 equiv.)MeOH
2.
1st Purification through
Activated Carbon filtration
EtOAcHClaq
1. SiliaMetS Thiol 30 % w/wEtOAC
50°C, 5 - 6 h
3. solvent swap, crystallization
2. filtration
Intermediate SRecovery : 95 %Pd content : under 20 ppm(1.2 equiv.)
OB
O**
Dark brown in colorPd content : around 1,000 ppm
OB
O**(1.0 equiv.)
2nd Purification throughsame Activated Carbon pad
Experimental procedure • In a 5 L three-neck-flask was introduced 1,93 L of methanol (HPLC grade), Pd(OAc)2 (21.38 mmol), PPh3 (29.50 mmol) and Cs2CO3
(1,105 mmol).The reactor was purged with argon, while maintaining mechanical agitation. The iodobenzene compound (737.2 mmol) and the chiral diboron (884.7 mmol) were then added, while maintaining a slight argon stream.
• The mixture was stirred under inert atmosphere for 3 hours at 50°C, (starting iodide was totally consumed). Methanol was evaporated until approximately 1000 mL was left. A portion of 2,000 mL of ethyl acetate was added, and the organic phase washed with 1,100 mL of HClaq (4M).
• The obtained mixture was then used as is, to test different purification procedures / sorbents.
Albeit good recovery (95 %) and satisfying Palladium removal (< 20 ppm) obtained on a process scale of 50 - 100 Kg, one main issue was highlighted:
• The activated carbon filtration step showed to be inefficient, requiring high amount of Metal Scavenger in subsequent purification step, and thus increasing processing time. Improving the effectiveness of this step was required.
This one point was addressed as part of the optimization of this purification process on a 200 g scale.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology2
FIRST, ROUGH PURIFICATION: ACTIVATED CARBON FILTRATION
Preliminary tests in standard filtration conditionsOut of the four available activated carbons in E-PAK Cartridges, three were tested in a standard filtration procedure following the borylation reaction.
Pd Scavenging Following Carbons Filtration (Initial [Pd]: 4,280 mg/kg)
Filtration Purification Conditions Pd Concentration (mg/kg) Scavenging (%)
C-941 Filtration - 1st passage 866 80
C-941 Filtration - 2nd passage 785 82
C-947 Filtration - 1st passage 739 83
C-947 Filtration - 2nd passage 640 85
C-948 Filtration - 1st passage 935 78
C-948 Filtration - 2nd passage 704 84
Experimental procedure • Following the borylation reaction work-up, 3 x 60 mL of the organic phase were filtered through 0.56 g of three different activated
carbon (C-941, C-947 and C-948) and rinsed with 12 mL of ethyl acetate.
• A 0.5 mL sample of each filtrate was collected, and analyzed by ICP-OES for Pd content.
• Each filtrate was washed again with 70 mL of aqueous HCl (4 M), and filtered through the same carbon filter cakes.
• A 0.5 mL sample of each filtrate was collected, and analyzed by ICP-OES for Pd content.
Conclusions• Although all three carbons gave similar results, C-947 showed slightly better scavenging performance.
• In all cases, the 2nd treatment improved the scavenging results to some extent.
• Hence, activated carbon C-947 was selected for the subsequent tests with E-PAK cartridges.
Optimized purification through C-947 Carbon E-PAK CartridgesA 5 x 1 cm C-947 (5 g) E-PAK cartridge was inserted in the appropriate housing (lab scale housing).
Pd Scavenging with a 5 x 1 cm (lab scale) C-947 E-PAK Cartridge (Initial [Pd]: 4,280 mg/kg)
E-PAK Purification Conditions Pd Concentration (mg/kg) Scavenging (%)
C-947 Filtration - 1st passage 655 85
C-947 Filtration - 2nd passage 510 88
C-947 Filtration - 3th passage 539 87
Experimental procedure • 150 mL of ethyl acetate (HPLC grade) was first used to pre-condition the unit.
• 525 mL of the crude solution was then passed through the cartridge at a 12.5 mL/min flow rate.
• Lastly, the cartridge was eluted three times at the same flow.
• At each passage, a 0.5 mL sample was collected and analyzed by ICP-OES for Pd content.
ConclusionTwo consecutive passes through a 5 x 1 cm C-947 E-PAK cartridge was shown to be sufficient to obviate a second HCl washing step and yield decreased Pd content.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology 3
SECOND, MORE TARGETED PURIFICATION: SILIAMETS METAL SCAVENGING
Preliminary tests in bulk conditionsScavenging screenings are the best way to start off with SiliaMetS functionalized resins. This is because even for the same functionality or metal, a variation in the scavenging efficiency can be observed depending on the nature of the products present in the solution to be treated. For example, steric hindrance, electronic effects, H-bond, all are factors that can greatly influence the scavenging %.
In order to determine the most suitable Pd scavengers for the current system, a screening was realized using 8 of our most suitable grafted silicas. Influence of temperature and reaction time were evaluated at the same time.
Pd Scavenging Screening for 1 h at r.t. (Initial [Pd]: 1,150 mg/kg)
SiliaMetS 10 % w/w (%) 20 % w/w (%) 30 % w/w (%)
SiliaMetS Cysteine 47 64 71
SiliaMetS Diamine 38 59 68
SiliaMetS DMT 67 91 97
SiliaMetS Imidazole 67 85 91
SiliaMetS TAAcOH 35 53 60
SiliaMetS Thiol 44 54 63
SiliaMetS Thiourea 68 93 97
SiliaMetS Triamine 21 33 40
Pd Scavenging Screening for 1 h at 50°C (Initial [Pd]: 1,150 mg/kg)
SiliaMetS 10 % w/w (%) 20 % w/w (%) 30 % w/w (%)
SiliaMetS Cysteine 53 71 78
SiliaMetS Diamine 51 68 78
SiliaMetS DMT 79 96 98
SiliaMetS Imidazole 76 90 94
SiliaMetS TAAcOH 46 56 64
SiliaMetS Thiol 50 59 69
SiliaMetS Thiourea 77 95 97
SiliaMetS Triamine 27 38 48
Pd Scavenging Screening for 4 h at r.t. (Initial [Pd]: 1,150 mg/kg)
SiliaMetS 10 % w/w (%) 20 % w/w (%) 30 % w/w (%)
SiliaMetS Cysteine 59 75 81
SiliaMetS Diamine 54 74 80
SiliaMetS DMT 83 98 99
SiliaMetS Imidazole 76 94 96
SiliaMetS TAAcOH 34 58 65
SiliaMetS Thiol 42 62 77
SiliaMetS Thiourea 86 98 99
SiliaMetS Triamine 16 39 42
CASE STUDY: Purification of a borylation reaction using E-PAK Technology4
Pd Scavenging Screening for 4 h at 50°C (Initial [Pd]: 1,150 mg/kg)
SiliaMetS 10 % w/w (%) 20 % w/w (%) 30 % w/w (%)
SiliaMetS Cysteine 51 75 81
SiliaMetS Diamine 57 74 80
SiliaMetS DMT 93 98 99
SiliaMetS Imidazole 83 94 96
SiliaMetS TAAcOH 47 58 65
SiliaMetS Thiol 51 62 77
SiliaMetS Thiourea 91 98 99
SiliaMetS Triamine 22 39 42
Experimental procedure • A 500 mL solution of 50 g of Intermediate S in ethyl acetate (HPLC grade) was made in a volumetric flask.
• In respect to Intermediate S: samples of 80 mg (10 % w/w), 160 mg (20 % w/w) and 240 mg (30 % w/w) of 8 different SiliaMetS were pre-weighed in 24 polypropylene tubes suited for SiliCycle’s MiniBlock® Platform.
• 8 mL of the above solution (containing 0.8 g of Intermediate S) was added to each tube.
• The MiniBlock Platform was orbitally shaken for 60 min. at room temperature, and sample of 0.5 mL of each solution were collected and filtered through 0.45 µm filters.
• The remaining solutions were shaken for 3 more hours and filtered off.
• All obtained samples (48) were analyzed by ICP-OES for Pd content.
• An identical manipulation was made at 50°C, generating 48 more samples to be analyzed.
Conclusions• SiliaMetS DMT and SiliaMetS Thiourea were shown to be the best scavengers for efficient Pd removal from this process stream.
• 20 to 30 % w/w of grafted silica was necessary to obtain satisfactory Pd scavenging.
• Increasing temperature and reaction time slightly improved scavenging performances.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology 5
Leaching investigationIn order to determine if any extractables had leached into the final product, the following experimentation was run.
Experimental procedure • Samples of 0.3 g of SiliaMetS DMT was suspended into 5 mL of ethyl acetate (HPLC grade), and shaken for 4 hours at room temperature.
• The suspension was filtered through a 0.45 µm syringe filter, evaporated and reconstituted in 1 mL of methanol (HPLC grade).
• A blank sample was also assayed.
• LC-MS (ESI+) was run on both samples. No extractables were detected by LC/MS/MS.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1961 120 180 240 299 359 419 479 538 598 658 717 777 837 896 956 1016 1076 1135
0.0
2.0e7
4.0e7
6.0e7
8.0e7
1.0e8
1.2e8
1.4e8
1.6e8
1.8e8
2.0e8
2.2e8
2.4e8
2.6e8
2.8e8
2.9e8
Inte
nsity
, cps
Time, min
Reagent blank
SiliaMetS DMT in ethyl acetate
Optimized purification through SiliaMetS DMT E-PAK CartridgesFollowing previous results, E-PAK purification was conducted under 20 and 30 % w/w conditions.
Pd Scavenging Following Each Elution (Initial [Pd]: 1,103 mg/kg)
SiliaMetS 20 % w/w Pd Concentration (mg/kg)
20 % w/w Scavenging (%)
30 % w/w Pd Concentration (mg/kg)
30 % w/w Scavenging (%)
1st elution 333 70 304 74
2nd elution 243 78 248 78
3th elution 180 84 173 85
4th elution N/A N/A 132 89
5th elution N/A N/A 93 92
6th elution N/A N/A 69 94
7th elution N/A N/A 53 95
Experimental procedure• A 5 x 1 cm SiliaMetS DMT (8 g) E-PAK cartridge was inserted in the appropriate housing (laboratory scale).
• 150 mL of ethyl acetate (HPLC grade) was first used to pre-condition the unit.
• Solution S was prepared adding 40 g of Intermediate S to 200 mL of ethyl acetate in a volumetric flask. A 0.5 mL sample was retrieved for subsequent ICP-OES analysis.
• The entire solution was passed through the cartridge at a 12.5 mL/min flow rate.
• Lastly, the cartridge was eluted three times at the same flow.
• Samples of 0.5 mL were collected after each run, and analyzed by ICP-OES for Pd content.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology6
A similar experiment was run following a 30 % w/w ratio (acc. to preconditionned E-PAK SiliaMetS DMT).
• Hence, 133 mL (26.6 g of Intermediate S) of Solution S was passed through a new E-PAK SiliaMetS DMT at 12.5 mL/min flow.
• Lastly, the cartridge was eluted 7 times at the same flow.
• Samples of 0.5 mL were collected after each passage, and analyzed by ICP-OES for Pd content.
Conclusions20% w/w was sufficient to achieve maximal scavenging of Pd.
Side reaction investigationFinal products obtained above were analyzed by LC-MS (ESI-), along with a sample of intermediate S. Methanol (HPLC grade) as a blank sample was also tested.
ConclusionNo new product was detected.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1961 120 180 240 299 359 419 479 538 598 658 717 777 837 896 956 1016 1076 1135
Time, min
0.0
5.0e6
1.0e7
1.5e7
2.0e7
2.5e7
3.0e7
3.5e7
4.0e7
4.5e7
5.0e7
5.5e7
6.0e7
6.5e7
6.9e7
Inte
nsity
, cps
Methanol (HPLC grade) Intermediate S E-PAK SiliaMetS DMT elution (20 % w/w) E-PAK SiliaMetS DMT elution (30 % w/w)
Final Conclusions
• All tedious & time consuming steps of the initial traditional purification protocol could be avoided:
1. 1st filtration on activated carbon followed by washings with fresh ethyl acetate
2. 2nd washing of the obtained organic phase with HClaq (4 M)
3. 2nd filtration on activated carbon followed by washings with fresh ethyl acetate
4. Treatment with 30 % w/w of SiliaMetS Thiol at 60oC for 6 h
5. 3th filtration, followed by ethyl acetate evaporation
6. Recrystallisation from cold heptane
• Activated carbon C-947 provided the best scavenging results among all three tested carbons.
• Two consecutive passes through an E-PAK C-947 cartridge obviated a second HCl wash.
• Treatment of the Intermediate S with 20 – 30 % w/w of SiliaMetS DMT in bulk mode at room temperature provides a good way to get rid of over 98 % of Pd.
• Similar results were obtained when the compound was filtered through an E-PAK SiliaMetS DMT cartridge (20 – 30 % w/w of SiliaMetS DMT) at room temperature, but from an experimental point of view, the modus operandi with E-PAK cartridges may be considered as a much more user friendly procedure and great alternative to avoid the presence of insolubles in reactor.
SiliCycle can help you design, scale up & optimize metal removal processes. Contact us at [email protected]
CASE STUDY: Purification of a borylation reaction using E-PAK Technology 7
E-PAK Cartridges PortfolioLab ScaleLab scale cartridges are designed to facilitate the evaluations of small samples. Testing with loose media can be done with samples as small as a few milliliters and are normally done in advance of cartridge testing to identify the formula offering the best results.
Lab Scale Cartridges
Cartridge Size Diameter x Height Flow Rate Range Pressure Drop ∆P (Psig)
with w/1 cps Fluid
Media Weight
SiliaMetS & SiliaBond SiliaFlash, Florisil & Activated Carbons
5 x 1 cm 5 - 100 mL/min ≤ 7.5 psig 8 g 5 g
5 x 10 cm 50 - 500 mL/min ≤ 5 psig 75 g 50 g
5 x 25 cm 125 mL/min - 1 L/min ≤ 5 psig 200 g 125 g
Pilot & Commercial ScaleE-PAK pilot scale cartridges provide rapid processing for volumes from 10 to hundreds of liters, and can establish the parameters for larger scales, since E-PAK offer linear scalability.
E-PAK commercial scale cartridges provide rapid processing for manufacturing operations needing to process batch sizes of > 10,000 liters or can be adapted for continuous operation.
Pilot & Commercial Scale Cartridges
Cartridge Size Diameter x Height Flow Rate Range Pressure Drop ∆P (Psig)
with w/1 cps Fluid
Media Weight
SiliaMetS & SiliaBond SiliaFlash, Florisil & Activated Carbons
Pilot Scale
16.5 x 12.5 cm 0.95 - 2.5 L/min ≤ 10 psig 875 g 850 g
16.5 x 25 cm 1.9 - 5 L/min ≤ 10 psig 1.75 kg 1.7 kg
Commercial Scale
16.5 x 50 cm 3.8 - 10 L/min ≤ 10 psig 3.5 kg 3.4 kg
16.5 x 100 cm 7.6 - 20 L/min ≤ 10 psig 7 kg 6.8 kg
Both Pilot and Commercial cartridges are provided with a Code 8 (closed top & open bottom end caps-bottom with double 2-222 Teflon® encapsulated Viton® o-ring) cartridge sealing configuration.
To meet commercial processing requirements, E-PAK cartridges can be operated in line or in parallel for increased capacity.
STRATEGY FOR FINE-TUNING THE PURIFICATION PROCESS
Combination of an initial, rough purification with activated carbon together with a second metal scavenging protocol is a very powerful purification strategy.
Yet, even with good purification results in hand, the scale-up of these conditions from R&D to process laboratories, all the way to industrial scales remains a huge challenge.
Created with proprietary technology, E-PAK radial flow adsorption cartridges provide rapid adsorption kinetics and processing capacities suitable for all purification scales: laboratory, pilot and commercial operations.
CASE STUDY: Purification of a borylation reaction using E-PAK Technology8
SiliCycle E-PAK cartridges are available packed with three different activated carbons (C941, C947, C948) and six different silicas (SiliaFlash Bare Silica, SiliaMetS Thiol, SiliaMetS DMT and SiliaMetS Amine, Diamine, Triamine).1
Activated carbons and bare silica gels are useful for the removal of various impurities, metallic and organic, as well as pigments, and volatile compounds, whereas functionalized resins are extremely specific to given metals or organics:
SiliCycle’s Scavengers for E-PAK Cartridges
Scavenger Structure Description
Scavenger for:
Typically Scavenges
Met
als
Elec
troph
iles
Nuc
leop
iles
Ioni
c Bo
ndin
g
PGI *
SiliaMetS Thiol PN: R51030B
Loading: ≥ 1.20 mmol/g Endcapping: yes Solvent Compatibility: All
Si SH
SiliaMetS Thiol is our most versatile and robust metal scavenger for a variety of metals under a wide range of conditions.
Ag, Hg, Os, Pd & Ru Cu, Ir, Pb, Rh, Se & Sn
SiliaMetS DMT PN: R79030B
Loading: ≥ 0.50 mmol/g Endcapping: yes Solvent Compatibility: All
Si NH
N
NN
SH
SH
SiliaMetS DMT is the silica - bound equivalent of 2,4,6 - trimercaptotriazine (trithiocyanuric acid, TMT). It is a versatile metal scavenger for a variety of metals and the preferred metal scavenger for ruthenium catalysts and hindered Pd complexes (i.e. Pd(dppf)Cl2).
As, Ir, Ni, Os, Pd, Pt, Rh, Sc,Ru & Se Cd, Co, Cu, Fe, Sc & Zn
SiliaBond Amine PN: R52030B
Loading: ≥ 1.20 mmol/g Endcapping: yes Solvent Compatibility: All
Si NH2
Also known for their electrophile scavenging efficiencies and their base reagent qualities, SiliaMetS Amine, Diamine and Triamine have proven to be very useful for the scavenging of the following metals: Pd, Pt, Cr, W and Zn.
Cd, Cr, Pd, Pt, Rh & Ru Co, Cu, Fe, Hg, Pb, W & ZnAcid chlorides, Aldehydes, Anhydrides, Chloroformates, Isocyanates, Ketones, Sulfonyl ChloridesAcids & Acidic Phenols
SiliaMetS Diamine PN: R49030B
Loading: ≥ 1.28 mmol/g Endcapping: yes Solvent Compatibility: All
Si NH
NH2
Cr, Pd, Pt, W & Zn Cd, Co, Cu, Fe, Hg, Ni, Pb, Ru, Se, V & ScAcid chlorides, Aldehydes, Anhydrides, Chloroformates, Isocyanates, Ketones, Sulfonyl ChloridesAcids & Acidic Phenols
SiliaMetS Triamine PN: R48030B
Loading: ≥ 1.11 mmol/g Endcapping: yes Solvent Compatibility: All
Si NH
NH2
HN
Cr, Pd, Pt, W & Zn Ag, Cd, Co, Cu, Fe, Hg, Ni, Os, Pb, Rh, Ru & Sc
Acid chlorides, Aldehydes, Anhydrides, Chloroformates, Isocyanates, Ketones, Sulfonyl ChloridesAcids & Acidic Phenols
* PGI: Potentially Genotoxic Impurities
1 More SiliaMetS in E-PAK Cartridges to come soon!
CASE STUDY: Purification of a borylation reaction using E-PAK Technology 9
Scale-UpOne of the strongest benefits of SiliCycle E-PAK Cartridges is their linearity upon scale-up. As shown below, in a typical Suzuki-Miyaura coupling for which palladium needed to be removed, each format behaved very similarly in terms of efficiency (scavenging %), kinetics and relative capacity.
NH
Br
COOEt +
tBu
B(OH)2
Pd(OAc)2,P(o-tol)3,
HCO3,i-PrOH, H2O
NH
COOEt
tBu
Experimental Conditions
E-PAK Format Bead volume (mL)
Flow rate (mL/min)
Residence Time (min:sec)
5 cm x 1 cm 18.8 10 01:53
5 cm x 12 cm 188 100 01:53
5 cm x 25 cm 470 250 01:53
16.5 cm x 25 cm 4,750 2,600 01:50
16.5 cm x 100 cm 19,000 10,400 01:50
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Sca
veng
ing
Effic
ienc
y (%
)
Number of Recirculation Cycles
5 cm x 1 cm
5 cm x 10 cm
5 cm x 25 cm
16.5 x 25 cm
16.5 x 100 cm
Once the best purifications sorbents have been identified in bulk, transferring the conditions from bulk to cartridges can be a very robust strategy for rapid and efficient scale-up.
Scale-Up CalculationAlthough there are always exceptions, scale-up projections based on a linear extrapolation of adsorbent mass have proven to be quite accurate when test conditions including contact time, temperature, solvent type and contaminant and compound levels are held constant. The following table shows the scale-up/relative change in mass between lab, pilot and commercial size E-PAK cartridges.
Scale-Up calculation for Silica-Based Adsorbents
Cartridge Sizes 5 x 1 cm 5 x 10 cm 5 x 25 cm 16.5 x 12.5 cm 16.5 x 25 cm 16.5 x 50 cm 16.5 x 100 cm
Scale-up Factor - 10 25 80 220 440 875
Mass of Silica (g) 8 75 200 875 1,750 3,500 7,000
# mmol SiliaMetS Thiol (1.3 mmol/g) 10.4 98 260 1,138 2,275 4,550 9,100
# mmol SiliaMetS DMT (0.6 mmol/g) 4.8 45 120 525 1,050 2,100 4,200
# mmol SiliaBond Amine (0.2 mmol/g) 9.6 90 240 1,050 2,100 4,200 8,400
# mmol SiliaMetS Diamine (0.26 mmol/g) 10.2 96 256 1,120 2,240 4,480 8,960
# mmol SiliaMetS Triamine (1.11 mmol/g) 8.9 83 222 971 1,942 3,885 7,770
Bead volume (cm3) 18.8 188 470 2,375 4,750 9,500 19,000
Flow Rate Range (mL/min) 7.5 75 190 950 1,900 3,800 7,600
Flow Rate Range (mL/min) 1 - 20 10 - 200 25 - 500 100 - 2,500 250 - 5,000 500 - 10,000 1,000 - 20,000
Conditionning 150 mL 600 mL 1.35 L 7.5 L* 15 L 35 L* 70 L
* Estimated data
Measurement Methodology:• Scale-up Factor: mass of silica / 8 g (smallest size)• Mass of Silica (g): upon packing of cartridge• # mmol SiliaMetS XXX (X.X mmol/g): silica mass x typical loading of SiliaMetS / SiliaBond• Bead volume (cm3): cake total volume, excluding cap, including middle hole• Recommended Flow Rate (mL/min): for residence times of 2.5 minutes• Flow Rate Range (mL/min): for residence times from 1 to 20 minutes• Conditionning: 3 x Tank volume including cartridge
E-PAK® : FLOW CARTRIDGES FOR METAL REMOVAL NEW
METAL & ORGANIC SCAVENGING
CATALYSIS & SYNTHESIS
• Eliminates the use of insoluble particulates in reactors
• High adsorption capacity & flow rate• Various sizes available for easy scale‑up
from lab to industrial scale
Removal of:• Metals• Electrophiles & Nucleophiles• Potential Genotoxic Impurities (PGI)• Other organic residues
• Couplings (Suzuki, Stille, Heck, ...)• Debenzylations & Hydrogenations• Oxidations• And Many More Reactions
SAMPLE PREPARATION
HIGH PRESSURE CHROMATOGRAPHY
LOW PRESSURE CHROMATOGRAPHY
• SPE & Well Plates• Micro‑SPE Tips• QuEChERS & FaPEx NEW
• SPE Hardware & Manifold
• Bulk Sorbents• HPLC Columns• SFC Columns• Guard Cartridges & Accessories
• Bulk Silica Gels (Irregular & Spherical)• Bonded Phases• TLC Plates• Pre‑packed Flash Cartridges
EXTRACTION & PURIFICATION NEW
R&D SERVICES
• Extraction & Purification Services• Essential Oils & Hydrosols• Purified Natural Extracts• Probiotics & Bacteriocins
• Scavenging Screening• Method Development & Optimization• Impurities Identification• Custom Column Packing
Founded in 1995, SiliCycle® is specialized in high value silica‑based and specialty products for chromatography, analytical and organic chemistry and purification.
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