The recording of Cannabis Tech Media's recent webcast on Ultrasonic Liquid Processing for Cannabis Oil Nano-Emulsification and Extraction, featuring guest speaker Dr. Alexey Peshkovsky, President and Chief Scientific Officer of Industrial Sonomechanics, is now ready. The webcast, which was held on Thursday, May 17th, 2018, had over 300 registered participants and generated close to 150 questions. Some of these questions were addressed by Alexey during the webcast. The answers to the rest are provided in this post. If you have any additional questions, please do not hesitate to contact us or leave a comment below.
Webcast Recording:
Webcast Questions & Answers:
1. Can you go over some of the encapsulation methods, specifically liposome tech?
I covered some of the differences between nanoemulsions and liposomes during the webcast. Further information on this subject is available in this article: http://blog.sonomechanics.com/blog/water-soluble-cannabis-oil-microemulsion-liposomes-or-nanoemulsion
2. This technology will allow cannabinoids to become water soluble?
Yes, although I prefer the term "water-compatible" for the reasons provided in the webcast.
3. So does your technology not need surfactants?
Some amount of food-grade surfactant(s) is still required (less than the total amount of oil that is nano-emulsified). It is, however, much lower in comparison to the amount of surfactants required to make a microemulsion.
4. We are working with your machines to emulsify cannabinoids. How can we encapsulate the finished liquid so it is stable in a capsule? So far, all attempts have melted the cap.
This question was addressed during the webcast.
5. Do you recommend dual-phase systems like lecithin/solubilizer?
This question was addressed during the webcast.
6. How does nano emulsion compare to liposomes technology?
I covered some of the differences between nanoemulsions and liposomes during the webcast. Further information on this subject is available in this article: http://blog.sonomechanics.com/blog/water-soluble-cannabis-oil-microemulsion-liposomes-or-nanoemulsion
7. How does the crystallization process work with this equipment?
We do not have a crystallization process developed for the cannabis industry.
8. What would be the most natural surfactant option available?
The best natural surfactant, in my opinion, is Quillaja Saponin available under the brand name of Q-Naturale. Unfortunately, it is quite bitter and does not yield translucent nanoemulsions.
9. Does your equipment require surfactant in an indirect sonication setup?
Some amount of food-grade surfactant(s) is always required (less than the total amount of oil that is nano-emulsified). To my knowledge, however, it is not possible to commercially produce stable nanoemulsions using an indirect sonication setup.
10. What is generally the amplitude of the barbell horns?
The maximum amplitude of Barbell Horns™ is 115 microns (HBHB-type, ISP-3000 ultrasonic processor). I recommend processing nanoemulsions at around 90 microns.
11. Can you discuss the demulsification capabilities of sonication?
They are similar to its emulsification capabilities but involve using demulsification agents instead of surfactants.
12. What is the size of the particles in your emulsions, and how was this measured? DLS, cry-TEM?
Between 20 and 40 nanometers (d50, volume distribution, CONTIN algorithm), measured by DLS.
13. We are told that some of the surfactants produce a very bitter end product. If so, what do you suggest?
Most surfactants (Q-Naturale, polysorbates, sorbitans, etc.) do have a very bitter taste. My suggestion is to consider our NanoStabilizer®-LT - it is practically tasteless and much more effective than these surfactants. This being said, the bitterness could also come from your cannabis extract or isolate. This topic was covered in the webcast.
14. What about solid core nano particles?
These can be made in a similar way as nanoemulsions, but using a carrier oil that is solid at the temperature below about 50 C.
15. Nanoemulsions are surface active. If you put it into a hydrophobic capsule, it can become unstable. What is the shelf life of your nanoemulsions in capsules/softgels?
Correctly made nanoemulsions are stable in the presence of hydrophobic surfaces. Translucent nanoemulsions produced with our ultrasonic processors and NanoStabilizer®-LT are permanently stable regardless of container material.
16. I'm wondering if water is detectable using Karl Fisher, FTIR, or DLS techniques?
I am not sure I understand why you would want to detect water in an oil-in-water nanoemulsion.
17. What is the size are you reaching/targeting?
Between 20 and 40 nanometers (d50, volume distribution, CONTIN algorithm), measured by DLS.
18. We are currently using Polysorbate 80 in our emulsions with one of your machines and it's working great. Was just wondering if that's a good one to use?
This question was addressed during the webcast.
19. We currently make CBD and THC emulsions with a 15,000 rpm high shear mixer. These emulsions are stable for 180 days. Can we post process these materials to make nanoemulsions?
Yes, emulsions produced with a high-shear mixer can generally be improved by high-amplitude ultrasonic processing. If the formulation allows it, they can be converted to permanently stable nanoemulsions.
20. What are the typical cannabinoid concentrations of your nanoemulsions? What is the typical surfactant concentration in those?
Stable milky nanoemulsions can be made with up to about 100 mg/ml of cannabinoids, 200 mg/ml of carrier oil (300 mg/ml total oil) and 30 - 50 mg/ml of surfactants. Translucent nanoemulsions can have up to about 50 mg/ml of cannabinoids, 100 mg/ml of carrier oil (150 mg/ml total oil) and 100 - 120 mg/ml of surfactants.
21. Can you explain some of the work you guys have done, with your equipment, related to extraction and refinement of oleoresins/ plant extracts? Do you see potential in doing water only extraction/ refinement or would some solvent(ethanol) be required?
Water-based extraction is currently in the R&D phase and, based on preliminary data, I believe we will be able to avoid using solvents entirely. This was addressed during the webcast.
22. Is it gras, the nano stabilizer?
Yes, all components are GRAS and derived from natural sources.
23. Does the nano-emulsification process work with multiple compounds at a time, or are there things one needs to be concerned about when mixing. Is it better to add other compounds later?
Yes, if your oil phase comprises several compounds (e.g., cannabinoids, terpenes, etc.), they can generally be nano-emulsified together. Alternatively, since nanoemulsions are miscible with each other, they can be made separately and mixed later.
24. Can you cover again the list of benefits of the cannabis nano-emulsion stabilizer?
NanoStabilizer®-LT was designed to simplify the ultrasonic production of high-quality, translucent nanoemulsions of bio-active ingredients such as cannabis extracts. The process requires you to have one of our ultrasonic processors, NanoStabilizer®-LT, distilled water, and an active ingredient (e.g., CBD or THC extract). We provide step-by-step processing instructions. Further information is available at:
http://blog.sonomechanics.com/blog/stabilizer-package-for-producing-water-soluble-cannabis-extracts
25. Is the nanoemulsifier safe in vaporization products?
Water-based nanoemulsions cannot be vaped with common devices. They can, however, be nebulized. The safety of NanoStabilizer®-LT in inhaled products has not been sufficiently studied yet, however.
26. Do you offer organic nanostabilizer options?
Our NanoStabilizer®-LT cannot be labeled as organic, although all its ingredients are GRAS and derived from natural sources. We do, however, offer an organic version of this product, NanoStabilizer®-LSO.
27. How do you process control for particle size uniformity? What size particles are found optimal?
When developing new formulations, we use Laser Diffraction and Dynamic Light Scattering droplet size measurement techniques. The nanoemulsions made with our technology generally have mean droplet sizes of about 20 - 40 nanometers (d50, volume distribution, CONTIN algorithm), which makes them highly translucent and very bioavailable. When following our methodology, our clients can simply rely on the translucency of their nanoemulsions as the main quality control parameter, as it is closely correlated with the mean droplet size and the tightness of size distribution. In most cases, repeated droplet size analysis is not needed once the process has been developed and product translucency has been achieved.
28. What is happening if the nano-emulsion gets cloudy in 24 or 48 hours?
I am told that you recently contacted us regarding this issue. You are using an ultrasonic processor that is not manufactured by us. It is hard to speculate what went wrong in your case because you are following a procedure designed only to be implemented with our ultrasonic processing equipment.
29. What is the labeling requirements for the stabilizer product?
Labeling requirements vary by country and state. You would need to check your local requirements.
30. What are the particle size range and concentration of your cannabinoid nanoemulsions?
Generally, between 20 and 40 nanometers (d50, volume distribution, CONTIN algorithm) for the cannabis extract concentration up to 50 mg/ml.
31. What are some examples of good antioxidants to use with cannabis nano emulsions?
This question was addressed during the webcast.
32. Using your technology, what is the maximum mg per ml of cannabinoids that could fit in a finished product without compromising optical translucency?
Translucent nanoemulsions can have up to about 50 mg/ml of cannabinoids.
33. What is the maximum possible concentration of cannabinoids in the emulsion? Based on the color or the emulsion, I assume that full plant extract can be used. Or are distillates/isolates required?
You can use almost any winterized and/or distilled cannabis extract - full plant oil, isolate, distillate, etc. Stable milky nanoemulsions can be made with up to about 100 mg/ml of cannabinoids. Translucent nanoemulsions can have up to about 50 mg/ml of cannabinoids.
34. How is this technology used to avoid/mask off flavors?
Our technology does not introduce of mask flavors. This question was further addressed during the webcast.
35. Are cannabis nanoemulsions bioactive via sublingual application?
Yes, they are very effective when applied this way.
36. Liters per/minute?
You can make between 5 and 10 L/hour with the BSP-1200 processor and NanoStabilizer®-LT. The ISP-3000 unit is about 4 - 5 times faster.
37. Is your Nano Stabilizer all-natural or organic?
NanoStabilizer®-LT cannot be labeled as organic, although all its ingredients are GRAS and derived from natural sources. We do, however, offer an organic version of this product, NanoStabilizer®-LSO.
38. Can both winterized cbd oil "full spectrum" and cbd isolate (99%) be used with this system? Combining their surfactant solution with both types of CBD?
Yes, you can use almost any winterized and/or distilled cannabis extract - full-spectrum oil, isolate, distillate, etc.
39. Can you go directly from sonication to tincture?
Yes, nanoemulsions can be used as water-based tinctures.
40. Is there a usp or nf monograph for the emulsifier?
No.
41. Could administering cannabinoids in nanoemulsions affect the distribution in the body, and ultimately the pharmacodynamics of the compounds?
Based on what we know from studies done on similar hydrophobic bio-active substances administered via nanoemulsions, there is a strong possibility that it could. More research is needed to answer this question fully, however.
42. How much is the smallest system?
Please follow this link to request an official quote: http://info.sonomechanics.com/contact_us
43. How about transdermal?
Yes, you can use nanoemulsions for transdermal applications.
44. One of the challenges that I have read about is that there are not many labs that have the ability to accurately analyze a nano emulsion so that 3rd party verification of nano contents is very difficult, and also inconsistent.
This is correct, although there are more qualified labs now than just a few months ago. The testing is normally done by HPLC coupled with mass spec and/or UV, and involves transferring (extracting) the active ingredients (cannabis extract, isolate, etc.) from the product to an organic solvent. While this step is easy for oil-soluble extracts, it is not necessarily so for water-compatible extract nanoemulsions. The laboratory doing the analysis must understand that the ingredients you are trying to analyze are dispersed in water in the form of stable nanodroplets, which must be destabilized to be fully transferred to the organic solvent phase.
45. Why are your emulsions using less surfactant more stable than traditional approaches to micro emulsions? What is your ratio of surfactant to CBD?
Micro-emulsification is a purely chemical approach, where large amounts of strong surfactants "solubilize" the oil (chemically break it up into nanodroplets). Nano-emulsification is a primarily mechanical approach, where nanodroplets are formed by ultrasonic cavitation-generated microjets, and the role of surfactants is mainly to maintain the droplets after they are already formed. This is significantly easier and allows for milder surfactants used in much smaller amounts. For more information, please see this article: http://blog.sonomechanics.com/blog/water-soluble-cannabis-oil-microemulsion-liposomes-or-nanoemulsion
With our technology, stable milky nanoemulsions can be made with up to about 100 mg/ml of cannabinoids, 200 mg/ml of carrier oil (300 mg/ml total oil) and 30 - 50 mg/ml of surfactants. Translucent nanoemulsions can have up to about 50 mg/ml of cannabinoids, 100 mg/ml of carrier oil (150 mg/ml total oil) and 100 - 120 mg/ml of surfactants.
46. Do you have any pharmacokinetic data for cannabinoid absorption?
Not at this time. We are currently working on it.
47. What about an oral spray rather than the standard oil dropper taken orally ?
Yes, nanoemulsions can be used as water-based oral sprays and are very effective.
48. Can this machine be used as an extractor, turning raw plant material into oil?
Yes, it can. More information is available here: http://blog.sonomechanics.com/blog/cannabis-concentrates-medical-significance-and-extraction-methods
49. Can you make an injectable serum?
Yes, nanoemulsions can be used as water-based injectable serums.
50. How stable are these nano-emulsions? Will they separate after a few hours, days, etc.?
They remain stable indefinitely if formulated correctly.
51. Do you get better skin penetration using your technology? If so, why?
Yes. Transdermal delivery of cannabinoids can be significantly enhanced with a novel formulation called "nano-emulgel", which is produced by entrapping an aqueous nanoemulsion of cannabis oil in a semi-solid colloidal network (hydrogel). See more here: http://blog.sonomechanics.com/blog/ways-to-consume-cannabis-how-nanoemulsions-can-help
52. Could you recommended a tasteless natural emulsifier/surfactant for beverage applications to nanoemulsify CBD?
Our NanoStabilizer®-LT is tasteless. It is derived from natural sources, although it cannot be labeled as "natural". The best natural surfactant, in my opinion, is Quillaja Saponin available under the brand name of Q-Naturale. Unfortunately, it is quite bitter and does not yield translucent nanoemulsions.
53. Are your surfactants within your Nano Stabilizer compatible to make a nanoemulsion to be used with a Nebulizer?
Translucent nanoemulsions can easily be nebulized. The safety of NanoStabilizer®-LT in inhaled products has not been sufficiently studied yet, however.
54. What ultrasonic frequencies do you use to create such small droplets?
20 kHz.
55. Would nano-emulsion ever be used in an oil (i.e. coconut oil) vs just water. Any changes in bioavailability?
Nanoemulsions are compatible with water, not oil. Cannabinoids dissolve in oil, which eliminates the need to nano-emulsify them in it.
56. I have seen many claims that nano emulsions are 600% to 1,000% more absorbed and therefore are 6x to 10x more effective than standard emulsions. Therefore, the extended claim is that you can use 6x-10x less ingredients to gain the same effect. Are there any independent clinical studies that confirm those claims?
Based on multiple studies done on similar hydrophobic bio-active substances administered via nanoemulsions, these claims are not unreasonable (albeit quite ambitious). At this point, however, they remain just that - ambitious claims backed only by indirect evidence. Before selling products based on these claims, I believe direct evidence must be collected. Otherwise, it is just irresponsible marketing.
57. Can this technology create a glycerin nanoemulsion as well as in water?
Yes, with this technology, nanoemulsions can be made in glycerin instead or in combination with water.
58. How well do you think a distributed nanoemulsified product would hold up under processes such as carbonation and pressurized beverage serving systems?
These processes should not affect the stability of concentrated or diluted nanoemulsions.
59. Can water in oil nanoemulsions be made using Sonomechanics?
Yes.
60. You started to answer the previous question of the difference between a nano-emulsion and a liposome. Could you complete that answer.
I covered some of the differences between nanoemulsions and liposomes during the webcast. Further information on this subject is available in this article: http://blog.sonomechanics.com/blog/water-soluble-cannabis-oil-microemulsion-liposomes-or-nanoemulsion
61. Are there any existing process patents that cover liposomal encapsulation or is it a standard that is open?
I'm not aware of any meaningful patents on this subject.
62. Can you powderize the nano emulsion liquid? I.e., CBD isolate to nano emulsion liquid, back to water soluble increased bioavailable powder?
Yes, it is possible to make nanoemulsions in a powderized form. The first step is to make the liquid nanoemulsion. The following steps are to add a solid hydrophilic excipient to the nanoemulsion (e.g., a type of sugar) and to spray-dry the resulting liquid. As water is removed, the excipient effectively replaces it, resulting in a solid gel powder, each particle of which contains oil nanodroplets dispersed in the solid excipient matrix. When added to a beverage, the excipient is dissolved, and the nanoemulsion is reconstituted.
63. Is it possible to make a water soluble powder with this equipment?
Addressed above.
64. What kind of filtration equipment is required with your ultrasonic equipment?
For translucent nanoemulsions, we recommend using a hydrophilic-membrane 220 nm pore-diameter sterilizing filter. Milky nanoemulsions with droplets in the range of 100 - 300 nm should be passed through a hydrophilic-membrane 450 nm pore-diameter filter.
65. What is the maximum mg per ml of cbd/cannabinoids that can fit without compromising optical translucency stability in a finished product?
Nanoemulsion concentrates can have up to about 50 mg/ml of cannabinoids and still remain translucent. They become transparent when further diluted by water.
66. Are there any informal or formal studies that demonstrate bioavailability, absorption of nanoemulsified products vs. non-nanoemulsified products?
There are many bioavailability enhancement studies done for nanoemulsions, such as the one mentioned in this webinar. I have not yet seen any for cannabis nanoemulsions specifically. We are working on this presently.
67. What is the difference in efficacy between Chylomicron vs Bloodstream absorption?
When chylomicrons are present in the absorptive cells of the small intestine, cannabinoids are directed to the lymphatic system, thereby bypassing the liver before arriving in the bloodstream. Without chylomicrons, the cannabinoids go to the hepatic portal vein bloodstream flowing directly to the liver. The efficiency of absorption is likely similar, however, the pharmacokinetic profile and the effects can differ substantially.
68. Ok for the amplitude but what about the frequency?
About 20 kHz.
69. How long processing at 80-90 micron to achieve nano?
With the BSP-1200 processor and NanoStabilizer®-LT, you can make about 5 L of nanoemulsion in 1 hour. At the cannabis extract concentration of 50 mg/ml, this represents 25,000 doses, 10 mg per dose. The ISP-3000 processor is about 4 times faster.
70. Is nanoemulsion heat tolerant? Alexey mentioned baking brownie and nano would remain active. Can a nanoemulsion be pasteurized?
Nanoemulsions can be pasteurized, but they may become destabilized if boiled. Baking is not a problem, however, because water (from gastric fluids) will be reintroduced after digestive consumption, which mostly reconstitutes the original nanoemulsion.
71. Can a nano product such as a beverage be tested for potency for cannabinoids with a standard lab test?
Yes if one has sufficient experience with nanoemulsions. The testing is normally done by HPLC coupled with mass spec and/or UV, and involves transferring (extracting) the active ingredients (cannabis extract, isolate, etc.) from the product to an organic solvent. While this step is easy for oil-soluble extracts, it is not necessarily so for water-compatible extract nanoemulsions. The laboratory doing the analysis must understand that the ingredients you are trying to analyze are dispersed in water in the form of stable nanodroplets, which must be destabilized to be fully transferred to the organic solvent phase.
72. How do you compare nanoemulsification by sonication with high shear homogenizer?
Sonication is much more effective. The following journal article describes some of the differences (see last page, before Conclusions): https://bit.ly/2MCiEf3
73. What is the most natural surfactant that can be used?
The best natural surfactant, in my opinion, is Quillaja Saponin available under the brand name of Q-Naturale. Unfortunately, it is quite bitter and does not yield translucent nanoemulsions.
73. If doing whole plant hemp extracts, which parts of the plant would you recommend to process with nano-emulsification?
Plant parts cannot be nano-emulsified. Only the already extracted oils or isolates can.
74. Is your method better than spray drying?
These methods have different objectives and are complimentary. Spray drying is done after ultrasonic nano-emulsification to convert the liquid nanoemulsion to a water-soluble powder.
75. If you are using a terpene profile will this solubilize them as well?
Yes, terpenes can be nano-emulsified together with (or separately from) cannabinoids.
76. Does Nanostabilizer®-LT contain phospholipids ?
Yes.
77. Can you use your equipment with hydrocarbon extraction?
Yes.
78. Can terpenes be extracted?
Yes.
79. Does the water need to be at a specific pH? If yes, then what is the optimal pH needed?
No.
80. How does sonication effect pressure in a hydrocarbon extraction?
This depends on the design of the corresponding equipment.
81. Are units available for lease/trials?
Yes/no. Please contact us for a quote at: http://info.sonomechanics.com/contact_us
82. Without recirculation using the ultrasonication horn equipment do you get the same droplet size as the ultrasonic circulation equipment?
Yes, with our equipment, the results are the same for both setups.
83. What type of filtration is needed?
For translucent nanoemulsions, we recommend using a hydrophilic-membrane 220 nm pore-diameter sterilizing filter. Milky nanoemulsions with droplets in the range of 100 - 300 nm should be passed through a hydrophilic-membrane 450 nm pore-diameter filter.
84. What is the price point of the equipment ?
Please contact us for pricing at: http://info.sonomechanics.com/contact_us
85. Could you discuss the best carrier oil choice, MCT vs other options?
This topic is covered in our blog post, available under this link: http://blog.sonomechanics.com/blog/the-role-of-carrier-oils-in-water-soluble-cbd-and-thc-formulations
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