June 04, 2018

47 Answers To Your Ultrasonic Liquid Processing Questions

During last month's live webcast, our host Ellis Smith and guest Alexey Peshkovsky, Ph.D., President of Industrial Sonomechanics, answered as many questions as time allowed. The following are answers to the remaining 47!



  1. Can you cover again the list of benefits of the cannabis nano-emulsion stabilizer? Answer: NanoStabilizer™ 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™, 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

  2. Is your Nano Stabilizer all-natural or organic in any way? Answer: NanoStabilizer™ cannot be labeled as organic, although all its ingredients are GRAS and derived from natural sources.

  3. Can a nano product such as a beverage be tested for potency for cannabinoids with a standard lab test? Answer: 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.

  4. Is Nanoemulsion Heat Tolerant? Alexey mentioned baking Brownie and nano would remain active. Can a nanoemulsion be pasteurized? Answer: 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.

  5. Can you go directly from sonication to tincture? Answer: Yes, nanoemulsions can be used as water-based tinctures.

  6. 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? Answer: 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.

  7. How do you process control for particle size uniformity? What size particles are found optimal? Answer: 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.

  8. What is the difference in efficacy between Chylomicron vs Bloodstream absorption? Answer: 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.

  9. Are there any informal or formal studies that demonstrate bioavailability, absorption of nanoemulsified products vs. non-nanoemulsified products? Answer: 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.

  10. Could administering cannabinoids in nanoemulsions affect the distribution in the body, and ultimately the pharmacodynamics of the compounds? Answer: 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.

  11. I have seen many claims that nanoemulsions 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?  Answer: 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.

  12. What is the maximum mg per ml of cbd/cannabinoids that can fit without compromising optical translucency stability in a finished product? Answer: Nanoemulsion concentrates can have up to about 50 mg/ml of cannabinoids and still remain translucent. They become transparent when further diluted by water.

  13. Can you powderize the nanoemulsion liquid? I.e., CBD isolate to nanoemulsion liquid, back to water-soluble increased bioavailable powder? Answer: 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.

  14. How about transdermal? Answer: Yes, you can use nanoemulsions for transdermal applications. Yes, nanoemulsions can be used as water-based oral sprays and are very effective.

  15. What about an oral spray rather than the standard oil dropper taken orally? Answer: Yes, nanoemulsions can be used as water-based oral sprays and are very effective.

  16. Can you make an injectable serum? Answer:  Yes, nanoemulsions can be used as water-based injectable serums.

  17. Can this technology create a glycerin nanoemulsion as well as in water? Answer: Yes, with this technology, nanoemulsions can be made in glycerin instead or in combination with water.

  18. Do you have any pharmacokinetic data for cannabinoid absorption? Answer: Not at this time. We are currently working on it. 

  19. Would nano-emulsion ever be used in an oil (i.e. coconut oil) vs just water. Any changes in bioavailability? Answer: Nanoemulsions are compatible with water, not oil. Cannabinoids dissolve in oil, which eliminates the need to nano-emulsify them in it.

  20. What about solid core nano particles? Answer: These can be made in a similar way as nanoemulsions, but using a carrier oil that is a solid at normal conditions.

  21. Are your surfactants within your Nano Stabilizer compatible to make a nanoemulsion to be used with a Nebulizer? Answer: Translucent nanoemulsions can be easily nebulized. The safety of NanoStabilizer™ in inhaled products has not been sufficiently studied yet, however.

  22. Could you recommend a tasteless natural emulsifier/surfactant for beverage applications to nanoemulsify CBD? Answer: Our NanoStabilizer™ 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.

  23. How stable are these nano-emulsions? Will they separate after a few hours, days, etc.? Answer: They remain stable indefinitely if formulated correctly.

  24. How well do you think a distributed nanoemulsified product would hold up under processes such as carbonation and pressurized beverage serving systems? Answer: These processes should not affect the stability of concentrated or diluted nanoemulsions.

  25. Why are your emulsions using less surfactant more stable than traditional approaches to microemulsions? What is your ratio of surfactant to CBD? Answer: 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.

  26. 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. Answer: 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.

  27. 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? Answer: Yes, you can use almost any winterized and/or distilled cannabis extract - full-spectrum oil, isolate, distillate, etc.

  28. Are cannabis nanoemulsions bioactive via sublingual application? Answer: Yes, they are very effective when applied this way.

  29. 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? Answer: 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.

  30. 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? Answer: 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.

  31. What are the typical cannabinoid concentrations of your nanoemulsions? What is the typical surfactant concentration in those? Answer: 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.

  32. 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? Answer: 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.

  33. 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? Answer: Correctly made nanoemulsions are stable in the presence of hydrophobic surfaces. Translucent nanoemulsions produced with our ultrasonic processors and NanoStabilizer™ are permanently stable regardless of container material.

  34. Does Nanostabilizer contain phospholipids? Answer: Yes

  35. Does your equipment require surfactant in an indirect sonication setup? Answer: 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.

  36. What would be the most natural surfactant option available? Answer: 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.

  37. We are told that some of the surfactants produce a very bitter end product. If so, what do you suggest? Answer: Most surfactants (Q-Naturale, polysorbates, sorbitans, etc.) do have a very bitter taste. My suggestion is to consider our NanoStabilizer™ - 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.

  38. Can you discuss the demulsification capabilities of sonication? Answer: They are similar to its emulsification capabilities but involve using demulsification agents instead of surfactants.

  39. You started to answer the previous question of the difference between a nano-emulsion and a liposome. Could you complete that answer?  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

  40. What kind of filtration equipment is required with your ultrasonic equipment? Answer: 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.

  41. How long processing at 80-90 micron to achieve nano? Answer: With the BSP-1200 processor and NanoStabilizer™, you can make 5 - 10 L of nanoemulsion in 1 hour. At the cannabis extract concentration of 50 mg/ml, this represents 25,000 - 50,000 doses, 10 mg per dose. The ISP-3000 processor is about 4 times faster.

  42. How do you compare nanoemulsification by sonication with high shear homogenizer? Answer: Sonication is much more effective. The following journal article describes some of the differences (see last page, before Conclusions): https://cdn2.hubspot.net/hubfs/478120/Pdf_documents/Nanoemulsion%20-%20Concepts,%20development%20and%20applications%20in%20drug%20delivery.pdf

  43. Is your method better than spray drying. Answer: 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.

  44. Can terpenes be extracted? Answer: Yes

  45. If you are using a terpene profile will this solubilize them as well? Answer: Yes, terpenes can be nano-emulsified together with (or separately from) cannabinoids.

  46. Can you use your equipment with hydrocarbon extraction? Answer: Yes

  47. What ultrasonic frequencies do you use to create such small droplets? Answer: 20 kHz.