Order of operations is also very important in any sort of emulsion based formulation. It’s best to mix your emulsifying agents with the part of the formulation that is going into the other.
In other words, if you’re putting CBD oil into milk, you are making an O/W emulsion, oil in water. So you will want to mix and dissolve your surfactants into the oil prior to mixing into the milk. I might suggest using as few emulsifying agents as possible as well. If you can hit your HLB value with only 2 emulsifying agents opposed to 3, you’ll be in better shape.
I also have to second the suggestions from @Soxhlet. Set up a proper DOE (design of experiment) and make several small batches, with small differences between each small batch to really see the effect certain parameters have.
Back in my pesticide formulation days, setting up a proper DOE to look at solubility of new active ingredients and different solvents and surfactants sometimes meant making up to 50 different 10-20mL formulations or prototypes to test very specific interactions or conditions.
on a different note, but still in line with the discussion, I have a strange but basic question. I get nano emulsions. Small particle sizes yada yada. But forgive my ignorance here, if a compound is dissolved in a solution, basically the solute is surrounded by the solution. Isn’t this, in theory nano on it’s own? If the solution chosen has a fast absorption rate wouldn’t you get the same effect as a nanoencapsulated emulsion?
I did a succesful nano prototype that hits pretty well.
100mL water into beaker. Stir on high on plate.
Gradually add 3.75g of Sucrose Ester and 1.25g PDPC
Stir at room temp for 30 mins. Heat to 60C, stir for 15 mins. Set aside.
3g Soybean Oil and 1g CBD isolate into separate beaker. Heat in oven at 190F for 15 minutes. Then put on hot plate, continuing heat, and Stir for 15min. Set aside while maintaining heat.
Heat up aquaeous phase to 52C. Stir. Surface tension should be almost like goo.
Drop hot organic phase into aquaeous phase at one drop every 5 seconds til done.
Place in ultrasonic cleaner bath for 30minutes.
Filter through .45um then .22um filters (PES syringe)
No creaming, ring, or separation yet. Milky white but dissolves into water very well. ~10mg/ml. Bitter since didnt add masking agents. But, I put 3ml into glass of water and wasnt bad.
Pleased overall. Going to keep trying to improve. Thoughts?
I’m pondering the same thing honestly. I am trying to do all this nano stuff to see what all the buzz is about. If I can skip all the o/w crap and just do homogenized mct or lct oil with noids and add the right stuff to get fast uptake thats on par with nano, yeah… id rather do that. No lie, this o/w nano business is hard stuff to do for an average guy like me.
Im not a biochem major, but technically if it has good solubility, and the solute has good/fast absorption, then I don’t see why it wouldn’t be as, if not more, effective. I don’t know is what happens to certain compounds in solution. Polymers, from what I gather when dissolved just kind of unbind and may still have linkages across the molecules making them bigger, but you could just hit it with the sonicater…
I’ve read some of your posts on MCT with noids thaf’s been homogenized with r/s homogenizer. Is it correct to say that a really well stirred MCT+Noid mixture is as effective, more, or nearly as effective in uptake and bioavailability as nanoemulsions? Since its all lipids and lipophilic noids, I’m wondering if stability isnt much of a concern. Been reading so mant damn books and articles lately, I can’t piece what the home message was lol.
Edit: All this is discussion of complexity of nanoemulsions vs simple lipid solutions, their tradeoffs, and their rewards.
I’ve used a high shear homogenizer to get my cannabinoids to my MCT. simple solution in lipids. anywhere from 5mg/ml up to 500mg/ml. effective. not particularly fast acting imo.
I do have both liquid and powdered gum acacia/lecithin formulations on the shelf, but those were made by my mentor, and I’ve never actually pressed him for the recipe. haven’t noticed greater bioavailability or faster uptake, but I don’t have potency data on the emulsions, so they could be twice as effective, and I would have no way of knowing that…
I think it makes sense to seek dissolution of the cannabinoids, from a mass transport perspective
maybe that’s less helpful though if your substance is dissolved in another hydrophobic phase like MCT? and fast absorption/onset is your goal
I was under the impression that the emulsion specifically being water-based is what might enable it to penetrate certain tissue (sublingual) well enough to cause quicker onset, by skipping first pass metabolism
You actually want to keep your mixture relatively cool. Not only will the energy from the sonicator naturally heat it up, but flocculation can occur due to the increased entropy between the “encapsulated active ingredient” from the added heat. The colloidal system works best with the most equal size distribution of micelles with the most equal distance distribution between micelles.
which is why its important to remember about electrical charges as much as the hlb system in itself.
And hlb is just “rule of thumb”. As you dive into all the variables even surfactant load is vital depending on the droplet size you wish to obtain. Small droplets mean more surface area, which mean more surfactant needed. A lot of surfactant suppliers like to boast about their low SOR, and while smaller droplets can be obtained with lower surfactant, those formed droplets may not be adequately covered and shelf life will suffer as a result. Stable emulsions not just have good polydispersity, but also good zeta potential.
here’s a good calculator to find an ideal SOR depending on droplet size/surface area Emulsion Surface Area | Practical Surfactants Science | Prof Steven Abbott.
Yes I can echo this. HLB is a great theoretical tool but you will notice that you can have completely different molecules in different classes of chemistry with the same HLB value. One would work for a certain application and the other wouldn’t.
Furthermore, one thing that seems to be consistent in almost all surfactant systems is that using a multi surfactant system tends to promote better long term stability than a single surfactant.
Another thing to keep in mind is that some values such as zeta potential really only mean something for ionic systems. If you are making a system completely comprised of non-ionic surfactants then the zeta potential may not reflect stability.
I have made THC nanoemulsions with a zeta potential that would normally be characterized as “very poor stability” but they have held up without any noticeable flocculation, separation, etc… I tend to use non-ionic surfactants in my nanoemulsions.
Yes, and to be frank its just as bitter as all the other ones on the market. Sonication time to 150nm about 25% quicker than Sonomechanics recipe. If your in cali or washington i can refer you to another companies product if youd like an idea of taste. feel free to DM