I’m about to foray into some medium scale chromatography (300ish grams). Working on separating some CBD and d8 off of a d9 heavy mix, 6’’ silica column.
I’ve watched a few basic videos. Done a few DCVC runs a while back. I know most of the basics. Just wanted to get some tips and tricks and techniques.
I did a first run on some messy distillate (85% cannabinoids, bit of a shit mix) to just try it out. Ran a 98% heptane 2% isopropyl solution.
I set it wet with heptane only, and rinsed with 1/2 column volume of heptane once it got into the silica.
I’m running under vacuum, it’s doing 3-4LPM through the column under about -10psi
Got some streaking, and a bit of separation towards the end of the run.
I was thinking my next run should use less isopropyl (1%?) To get better separation higher up? Or am I mixed up in my thinking?
Was going to strap a vibrator onto it for a bit, and tap it with something soft to settle it a bit more in hopes to avoid bleeding.
Packing the column is the most important part. Need to get the whole column flowing evenly. Using an ultrasonic bath while packing the silica makes it simple.
You’d get a lot less streaking if you reduced the diameter of your column too.
What diameter is your column? 300g is a lot of material. I recommend doing 50g at a time until you nail the separation. If your column diameter is sized appropriately, you will never need more than 6" of silica in your column.
Load your 6" of dry silica in, and add about 12-15" of your eluent into the column. Force solvent through with air/N2 as quickly as you can - this will remove air trapped between silica particles (you can reuse this eluent after your product is loaded on). Then dissolve an appropriate amount (again depends on column diameter) of your extract in your eluent and load it on top of the silica. Let it all adsorb into the silica. Then carefully add your eluent back so as to not disturb the top layer. Once your solvent is loaded back in, keep the eluent level/flow so that it proceeds down your column at at 2" per minute. You can take large fraction sizes running 50g at a time, maybe 150-200 mL fractions?
Look up this paper for more detail https://pubs.acs.org/doi/10.1021/jo00408a041
You will have to extrapolate your column diameter since he only provides suggestions on running 5g of material at a time. good luck!
I just wasn’t too sure if I’d get get proper cannabinoid separation with DCVC, and I did like the idea of single solvent system for ease of production (a bit more set and forget)
Smallest chroma cartridge I’ve ran is probably the 10g or 12g biotage flash carts.
For solvent system method confirmation. Then scaleup to 50g-120g carts for the actual R&D testing phase where we can run 2g-5g extract at a time, leaving you enough final products to do potency analysis easily.
Alot of basic chromatography sequences used in cannabis at a larger scale were discovered running the exact processes at the scales I listed above.
I’ve got a 12” by 48” buchner for the task. I’m really curious to see what kind of output you get. I wonder if I can do a kg on this with a bucket load of silica
Guess improving the packing is all you can really do then. Im pretty sure I read that industrially, pre-made chromatography columns are made by dry packing the media using pressure to feed the media into the column while sonicating the column. They also use perfectly spherical silica gel particles in a range of different particle sizes.
