INFORM March 2025

16 • inform March 2025, Vol. 36 (3)

40 35 30 25 20 15 10

Lecithin + lipophilic linker + hydrophilic linker

D60 SMEDDS (60 vol% surfactant 40 vol% oil)

Ibuprofen in D60 SMEDDS

D60 SMEDDS dilution

2-phase boundary

Ibuprofen suspension

Plasma conc. ug/ml

5 0

HLD-NAC predicted

0 100

200 300 400

500

2 phase region μ E + oil

Time, min

Simulated intestinal fluid

Ethyl caprate + ibuprofen

Demonstrating ibuprofen-loaded SMEDDS are fully dilutable and measuring ibuprofen absorption in vivo. Source: Nouraei, et al. , IJPharm , 610, 121237, 2021.

Cannabinoids are insoluble and have very low bioavail ability (6-12 percent). Using the SMEDDS technology, Micellae has developed a unique absorption-enhancing solution that uses lecithin and other plant-based surfactants in lieu of PEG based surfactants, making theirs the first and only self-dispers ing, fully water-dilutable SMEDDS made entirely of food-grade, plant-based excipients. Their proprietary formulation platform is called O2W, for oil to water. The animal study data on O2W showed promising results on significant reduction of onset time and increase in CBD absorption. “Initially, our focus was on making cannabinoids more sol uble in consumer products like beverages, water-based tinc tures, gummies, and topicals for recreational and wellness uses,” said Nouraei. “However, we have since shifted to lever aging our technology for pharmaceutical applications.” In collaboration with ears, nose and throat specialists at University of Toronto hospitals and the University Health Network, Micellae developed a “fast muco-penetrating” lipid nanoparticle (MP-LNP) intranasal formulation of CBD to treat chronic rhinosinusitis. The promising results from preclinical studies support advancing to a phase 1 clinical trial. O2W is available as a preconcentrate SMEDDS, as a partially diluted SMEDDS, as a diluted microemulsion, as a microencap sulated SMEDDS in solid-state powder form, and as a semi-solid gel. It enhances the speed and extent of CBD absorption, which is essential; a big problem with conventional cannabis edibles is that people do not feel the effects for as long as hours after ingestion, which can lead to overdosing. With Micellae’s O2W formulation, plasma concentration in rats peaks twenty to thirty minutes after ingestion, and people have reported feel ing effects within fifteen minutes or less. This was much quicker than when cannabinoids were delivered via the more standard carriers, olive oil and MCT (medium chain triglyceride) oil. Moreover, about half as much of CBD’s main second ary metabolite, 7-COOH-CBD, was produced in rats fed with

O2W-enhanced CBD compared to rats fed with CBD-MCT. This suggests that CBD delivered via O2W has a higher degree of lymphatic absorption and reduced metabolism in the liver. This can reduce the risk of liver damage sometimes associated with CBD and its metabolites and can also alleviate CBD’s potential drug-drug interactions with the many pharmaceuticals that are metabolized in the liver, especially among chronic users. Because microemulsions, in contrast to nanoemulsions, are thermodynamically stable, O2W-enhanced cannabis-in fused beverages and gummies are shelf stable for over six months to a year at room temperature, as is the undiluted O2W water-free concentrate loaded with CBD. O2W is sta ble in liquids with pHs ranging from 2 (like Coke, Sprite, and 7Up) up to 8 (like alkaline water). It retains its stability through ultra-high-temperature pasteurization, gradual increases of temperature from room temperature to 100 o C, and through multiple cooling and heating cycles. And long-term toxicology studies in rats indicated that it is safe. “We use all plant-based components–oils, polyglycerols, lecithins, and terpenes–but in different ratios,” Nouraei said. “We mix and match ingredients and ratios. The formulation is customized for each application: beverages are different from capsules are different from gummies.” Nouraei stressed that their technology can be used to enhance the delivery and bioavailability of any lipophilic com pound, ranging from pharmaceuticals to nutraceuticals, cos metics, and even agricultural active ingredients, in forms ranging from tablets, capsules, topical, and transdermal creams or patches, to nasal rinses and sprays. Diana Gitig earned her PhD in cell biology and genetics from Weill Cornell Graduate School of Medical Sciences in New York City. She writes about cell and molecular biology, immunology, neuroscience, and agriculture for arstechnica.com. She can be reached dmgitig@gmail.com.