SMEDDSs are mixtures of surfactants, linkers, and oils that, upon dilution with an aqueous phase, form microemulsions with sizes often ranging from 10-100 nm.
The smaller droplet size of SMEDDSs, compared to self-emulsifying drug delivery systems (SEDDSs), gives them a larger surface area to volume ratio and enables the transport of microemulsions through tight pores. View comparative table.
FIRST GENERATION vs NEXT GENERATION DDSs
First Generation PEG-Based
Limited increase in absorption and extensive metabolism in liver results in poor increase in potency and onset of action
Potential long-term safety concerns resulting from the use of PEGs and first-pass liver metabolism of CBD and THC
The use of PEGs and complex production processes create environmental concerns
Next Generation Fully-Dilutable PEG-Free
Significantly increased absorption and increased lymphatic transport results in higher potency and better onset of action
PEG-free, food-grade formulation increased lymphatic transport improves long-term safety
PEG-free, simple and low energy manufacturing makes it the environmentally friendly choice
The efficiency of O2W Powder and O2W Concentrate on improving the oral bioavailability of CBD compared to traditional CBD Oil Solution was demonstrated in a single-dose pharmacokinetic study in rats.
The pharmacokinetic parameters of Area Under the Curve (AUC), maximum Concentration (Cmax) and time where the maximum concentration is reached (Tmax) were all significantly increased. This clearly demonstrates greatly improved bioavailability of CBD at an unmatched speed. The results of the first four hours of the study are shown below:
What is the significance of the much shorter Tmax?
Whether it’s for pain management or recreational use, this means that the patient/ consumer will not have to wait to feel the effects
Reduces the risk of overdose due to delayed response with traditional products
Has any other drug delivery technology achieved similar results?
Tmax achieved with O2W is similar to the Tmax achieved with sublingual products, without the concerns associated with sublingual products such as inconsistent and unpredictable absorption from one individual to another and one application to another.
Pharmacokinetic Study with Ibuprofen
The efficiency of O2W Concentrate on improving the oral bioavailability of Ibuprofen compared to Ibuprofen Water Solution was demonstrated in a single-dose pharmacokinetic study in rats.
What this means: Higher absorption Rapid onset of action
How it works
MIMICKING NATURAL DIGESTION
1. Administration of O2W- enhanced cannabinoid containing capsule
2. Release of the content of the capsule in stomach while protecting the API (Active ingredient) from degradation by stomach acid and digestive enzymes
3. Spontaneous micellization when in contact with intestinal fluid creating nano- sized micelles encapsulating the API
4. Quick diffusion of the API- containing micelles across the intestinal unstirred water layer
5. Rapid and enhanced absorption of the API into both the lymphatic pathway and the systemic circulation (dual-absorption pathways)
6. Very fast onset, enhanced bioavailability and superior efficacy.
O2W-formulated capsules contain compact Reverse-Micelles. When the capsule is ingested, in contact with the water in the intestinal fluid, compact reverse micelles merge to make bigger reverse micelles. Reverse-Micelles will elongate to incorporate more water in the center, as the water content increases. At bicontinuous stage, there is equal amount of water and oil. The elongated micelle will merge to form the bicontinuous layers. As the water content increases, they disperse into elongated micelles and then micelles of less than 100nm size, which will deliver the “solubilized” active ingredient to the intestines, where they will be easily absorbed by the body.
Micelles are colloidal particles composed of amphiphilic molecules (molecules that have hydrophilic heads and hydrophobic tails). In an aqueous solution, these molecules assemble into nanosized structures (spherical, ellipsoid, cylindrical, or unilamellar) with a hydrophobic core and hydrophilic shell (1,2). Other hydrophobic compounds, such as CBD, can be loaded into the hydrophobic core. Micelles demonstrate several desirable properties as drug carriers and are often used as pharmaceutical carriers for water-insoluble drugs (1).
Torchilin, V. P. Micellar Nanocarriers: Pharmaceutical Perspectives. Pharm. Res.24, 1 (2006).
Hanafy, N. A. N., El-Kemary, M. & Leporatti, S. Micelles Structure Development as a Strategy to Improve Smart Cancer Therapy. Cancers (Basel).10, 238 (2018).
There are several bioavailability-enhancing techniques, including Lipid-Based Drug Delivery Systems (LBDDSs), chemical modifications, crystal modifications, and inclusion complexes. However, non-LBDDS techniques have multiple potential downsides, including that they have complex processes, are cost and energy-intensive, result in low stability, and produce limited dosage forms (1). On the other hand, Micellae’s LBDDS technology, O2W, has a simple and inexpensive production process, is highly stable, and can be used to produce an unmatched variety of dosage forms. O2W was engineered to significantly enhance the solubility, bioavailability, and time of onset of fat-soluble compounds, including cannabinoids. Free of PEGs and medium/short-chain alcohols, O2W is the only self-dispersing and fully water-dilutable Self-Microemulsifying Drug Delivery System (SMEDDS) made with food-grade excipients.
Nouraei, M. An Introduction to Micellar Solubilization Technology. 1–11 (2020).
LBDDSs are composed of a variety of oils and oil-like ingredients, emulsifiers, and sometimes water (1). They can be liquid (emulsions, nanoemulsions, microemulsions (μE) and SEDDS/SMEDDS), solid (solid-liquid nanoparticles and solid SMEDDS), and semi-solid (organogels).
SMEDDSs are the most superior type of liquid LBDDSs based on several measures of overall performance. (Please see “What is a SMEDDS”) Emulsions are the largest in size (1-20 µm) and provide the lowest increase in bioavailability. Contrary to the name, microemulsion particles are much smaller in size than nanoemulsion particles and provide the highest increase in bioavailability. Furthermore, nanoemulsions require a large input of energy, necessitating complex and energy-intensive equipment to make them kinetically stable, whereas microemulsions (and SMEDDSs) are thermodynamically stable and can be formed in a simple mixing vessel (1). Self-emulsifying LBDDSs such as SEDDSs/SMEDDSs are isotropic mixtures of oil and surfactant/cosurfactant that spontaneously form nanoemulsions/microemulsions upon mild agitation in an aqueous solvent. SMEDDSs may be defined as a concentrated microemulsion or latent μE. Since SMEDDSs are also water-free they have higher stability and consequently, they have a longer shelf-life than diluted microemulsions (1).
Nouraei, M. An Introduction to Micellar Solubilization Technology. 1–11 (2020).
Self-Microemulsifying Drug Delivery Systems (SMEDDSs) are water-free concentrate systems of oil(s) and surfactant(s) that upon exposure to an aqueous phase (e.g., gastrointestinal fluid) with mild agitation, spontaneously form microemulsions that function as a carrier for drugs. (Please see “What is a SMEDDS”)
Microemulsions are thermodynamically stable, self-assembling, transparent/translucent, and optically homogeneous (but microscopically heterogeneous) dispersions of an aqueous phase and oil phase, stabilized by an interfacial film of amphiphilic molecules.
Solubilization Enhancement: Quick and thermodynamically favored micellization significantly enhances the solubilization of the active pharmaceutical ingredient (API).
Ease of Manufacturing and Scale-up: Self-microemulsification is a thermodynamically favored process that occurs spontaneously with little to no energy input. No homogenizers, no sonicators, no pump or sheers are needed! In contrast, for conventional emulsions, energy is needed to break down the oil droplets and to create new surfaces. However, due to the high surface energy, the droplets tend to merge again.
Smaller Dosage Forms and Longer Shelf-life: The absence of water in SMEDDSs enhances the stability and shelf-life of both the formulation itself, as well as the API, compared to microemulsions.
For other advantages of O2W, please see our “O2W Advantage” section.
Despite their effectiveness in increasing the solubility of poorly soluble ingredients, there are numerous challenges in formulating SMEDDSs that limits their wide-spread use. The two main challenges of designing SMEDDSs are achieving full-dilutability and using only food-grade excipients.
Full-dilutability, or phase continuity over dilution, is a key factor in designing SMEDDSs. Full-dilutability is the ability of a drug delivery system to produce formulations that can be dissolved in any volume without phase separation. Full-dilutability is important because oral administration results in serial dilutions of compounds within the digestive system, thus it is critical for the formulation to remain stable at any water volume for optimum absorption.
Engineering fully dilutable microemulsions with food-grade and alcohol-free compounds is particularly challenging due to the limited choices for surfactants. Currently available microemulsions/SMEDDS contain Polyethylene Glycols (PEG) and short/medium-chain alcohol compounds. It is important because PEGs are petroleum-based compounds that are widely used in cosmetics as thickeners, solvents, softeners, and moisture-carriers. PEGs are not environmental-friendly and may present long-term safety concerns. Our PEG-free, food-grade formulation improves long-term safety.
According to the Biopharmaceutics Classification System (BCS), the two major limiting factors for absorption of an active ingredient are solubility and permeability. Accordingly, the substances are classified into four groups of which type II and IV compounds are of particular interest.
Certain chemical compounds can provide immense therapeutic benefit in vitro but may not demonstrate the same efficacy in vivo. This poor efficacy in vivo can often be attributed to the poor water solubility and bioavailability characteristics. In fact, pharmaceutical drug pipelines are seeing a rise in poorly water-soluble and bioavailable drug candidates, necessitating an effective solution (1).
One of the most effective solutions to tackle solubility and bioavailability concerns are drug delivery systems. Drug delivery systems are specifically designed to optimize the desired therapeutic effect(s) of hydrophobic compounds by substantially enhancing their water solubility, permeability, and bioavailability (2).
Recently, drug delivery systems have started to garner attention from their ability to promote effective immunization in COVID-19 vaccines. Specifically, all COVID-19 mRNA vaccines are delivered using lipid nanoparticles (LNPs), which efficiently encapsulate, condense, and increase cellular uptake of mRNA to reach cell cytosol (3).
J, B., ME, B. & P, A. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J. Pharm. Sci. 98, 2549–2572 (2009).
Wen, H., Jung, H. & Li, X. Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges. AAPS J. 17, 1327 (2015).
Park, K. S., Sun, X., Aikins, M. E. & Moon, J. J. Non-viral COVID-19 vaccine delivery systems. Adv. Drug Deliv. Rev. 169, 137 (2021).
Studies suggest that cannabinoids have a wide range of benefits ranging from treating rare forms of epilepsy to reducing anxiety (1). However, cannabinoids are considered to have low oral bioavailability, with only 4%-12% being absorbed in the gastrointestinal tract and reaching the bloodstream. Given this, the need for an effective drug delivery system is paramount to increasing the bioavailability of cannabinoids. O2W is a water-solubilizing and potency enhancing drug delivery system designed to substantially increase the bioavailability of poorly bioavailable compounds, such as cannabinoids. O2W does not alter the cannabinoids chemically but instead acts as a vehicle to encapsulate the active ingredient and deliver it to its intended destination.
Pamplona, F. A., da Silva, L. R. & Coan, A. C. Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis. Front. Neurol.0, 759 (2018).
One of the important characteristics of O2W is its turnability. Based on the need of the client, we can deliver a wide range of release profiles (immediate, delayed, extended).
Our concentrate platform is high-potency and fast-acting, allowing for high bioavailability and a rapid onset of action. Our powder formulation platform is extra high-potency and tunable release, allowing for extra high bioavailability and tunable immediate, delayed, or extended release. Our gel formulation platform is high-potency and extended-release, allowing for high bioavailability and tunable controlled release. (Please see “Breakthrough Product Platforms”)
Some examples of final products include extra high-potency, tunable-release tablets; high-potency, fast-acting capsules; high-potency, tunable extended-release capsules; instant, high-potency concentrate drops; and more. (Please see “Unlimited Product Options”)
Micellae’s powder platform is based on the process of solidification of the O2W liquid platform in which fine liquid droplets are microencapsulated to combine the advantages of the conventional liquid SMEDDSs with those of the solid dosage forms.
Microencapsulation is the process of coating one or more active ingredients with a (mixture of) polymer(s), forming a shell, with the objective of providing a physical barrier between the active ingredient and other components of the product to protect it from environmental factors like humidity, light, and air.
In a simplistic form, a microcapsule is a small sphere with an inner core containing one or more active compounds covered with a coating material sometimes called shell, membrane, coat, or wall. The coating materials are usually polymers from natural or synthetic sources, selected depending on the compound to be coated, the characteristics desired in the final capsules, and the type of release required. Depending on the coating material, many triggers can be used to activate the release of the encapsulated compounds: temperature, pH change (enteric and anti-enteric coating), enzymatic activity, time, etc.
While the conventional microencapsulation process involves coating the active ingredients, Micellae’s microcapsule coats the droplets of the CBD-loaded liquid delivery system.
Solidification of SEDDSs affords a multitude of benefits compared to precursor liquid-SEDDSs, which can be summarised within the following categorical advantages:
Improved drug solubilisation and dissolution,
Controlled drug release, and
Industrial and commercial benefits (1)
First, it allows our clients to make formulated tablet or loose powder dosage forms, the favourite mode of administration by doctors and patients. Pre-encapsulation of the whole dose into capsules/tablets provides more accurate and precise dosing in comparison to administering a prescribed volume of a suspension using a syringe or spoon and allows us to create different release profiles (immediate, delayed, controlled). It also results in better patient compliance (i.e., it is generally preferred by adult patients to administer capsules/tablets rather than a liquid formulation). The ease of use and tunability of the platform brings unique advantages to this platform in addition to the advantages of our conventional liquid SMEDDS.
Furthermore, the solidification of SMEDDSs enables simpler handling and manufacturing processes using more economic and conventional equipment (better suited to large-scale production). Solidification imparts physicochemical stability and reduces production costs while retaining, or optimising, the pharmacokinetic benefits of liquid SMEDDSs. Additionally, it avoids drug-packaging interactions, potential leakage, and migration of the excipients into the capsule shell.
This approach has given successful results for the enhancement of solubility and bioavailability of a variety of BCS class II drugs with results significantly superior to those obtained with the pure drug during in vitro and in vivo studies. It enhances intestinal solubilisation and improves drug permeability.
It is useful to protect compounds from environmental factors like humidity, light, and oxygen. It is also useful to protect compounds that are orally administered and need to pass the gastrointestinal tract without being affected by the stomach pH and the enzymatic action. The resulting microcapsules are more stable products and easy to handle and transport, with extended shelf-life.
Joyce, P. et al. Solidification to improve the biopharmaceutical performance of SEDDS: Opportunities and challenges. Adv. Drug Deliv. Rev. 142, 102–117 (2019).
Yes, Micellae is based on 15 years of research and has performed both in vivo and in vitro studies.
In 2021, Micellae performed a single-dose pharmacokinetic (PK) study in rats through an independent CRO. This study demonstrated the efficiency of our O2W powder and concentrate formulations compared to a traditional CBD Oil Solution. The pharmacokinetic parameters of Area Under the Curve (AUC), maximum concentration (Cmax), and time where the maximum concentration is reached (Tmax) were all significantly increased showing a greatly improved bioavailability of CBD at an unmatched speed. (Please see “Unprecedented Performance”)
Micellae has also performed a single-dose PK study in rats comparing O2W-Ibuprofen concentrate and with Ibuprofen in water. We found a 4x higher AUC, 3.6x higher Cmax, and significantly shorter Tmax. (Please see “Unprecedented Performance”)
Micellae out-licenses our patent-protected O2W technology to our partners. We will manufacture the customized blank pre-mixed formulation (intermediate product) with the help of a co-packer and will sell it to the licensee. (Please see “Services”) You (the manufacturer/cannabis producer) will add the cannabis extract in your facility and integrate a simple mixing step to your manufacturing process. (Please see “Manufacturing”)
Micellae is a business-to-business company with the objective of becoming the most valuable partner of high-quality pharmaceutical, medical, and recreational cannabis producers. Our mission is to provide the most advanced Drug Delivery System to significantly improve the solubility and bioavailability of cannabinoids.
Micellae out-licenses our patent-protected O2W technology to our partners. If you are interested in partnering with us, the first step is to contact our team, indicating the product you would like to create or enhance. Based on your desired product and release profile, we can help you select the optimal product platform (concentrate, powered, or gel) and develop a pricing estimate.
Yes, Micellae’s technology has seven current patents and one patent pending. The patents were filed by Dr. Edgar Acosta and Dr. Mehdi Nouraei. They are property of the University of Toronto and have been filed with the US Patent Office (Please see “Patents”).
O2W’s long-term toxicity study demonstrated long-term safety in rats with β-Carotene. In this study, male Sprague-Dawley rats were fed either a regular diet with no SMEDDS (control group), a diet enriched with 1% SMEDDS, or a diet enriched with 5% SMEDDS (n=6/group). The SMEDDS was loaded with 1000 ppm β-carotene.
During the 6-week period, the animals were monitored both physically and psychologically. At the end of the 6-week period, body dimensions were measured with no significant differences between groups. Furthermore, blood and tissue samples were collected for analysis. A Complete Blood Test (CBT) showed white blood cells (lymphocytes, monocytes, and neutrophils) were in the normal range for all three groups, indicating that the diet has no adverse impact on the immune system. Furthermore, the red blood cell, hemoglobin, and hematocrit for the control were below the normal ranges, while the results for the two test groups fell within the normal ranges. When weighing organs, no significant differences were found except for the 5% SMEDDS diet kidney being smaller.
Free of Polyethylene glycols (PEGs) and medium/short-chain alcohols, O2W is the only self-dispersing and fully water-dilutable SMEDDS made with food-grade excipients.
WHY IS THIS IMPORTANT?
Environmental sustainability and safety First generation LBDDSs often use PEGs (controversial petroleum-based compounds) as surfactants. The production of PEGs produces pollutants and may leave trace amounts of toxic impurities.
Unlike first generation LBDDSs, O2W is made of glycerol esters of fatty acids. This not only improves the safety and environmental sustainability of O2W, but also increases cellular absorption according to recent studies (please see “First vs Next Generation DDSs”).
Dilutable microemulsions require a combination of surfactants, cosurfactants and cosolvents (alcohols). Alcohols such as ethanol are known to be toxic, largely due to membrane disruption effects.
Additionally, surfactant/alcohol synergy that facilitates nanoemulsion formations potentially increases nanoemulsion cytotoxicity if the surfactant is in sufficient excess.
Consequently, our alcohol-free, PEG-free O2W formulations provide significant advantages.
Full dilutability means a formulation can be dissolved in any volume without phase separation.
WHY IS THIS IMPORTANT?
Absorption is optimized Oral administration results in serial dilutions of compounds within the digestive system, thus it is critical for the formulation to remain stable in any water volume for optimum absorption.
O2W is a self-dispersing system that spontaneously forms a microemulsion upon mild agitation in an aqueous solvent.
The active ingredient will be solubilized by micellization in the body to a completely homogeneous microemulsion with mean droplet size of less than 100nm.
WHY IS THIS IMPORTANT?
Significant cost reduction In conventional emulsions, energy is required to break down the oil droplets and to create new surfaces. However, due to the high surface energy, the droplets tend to merge again. In contrast, self-microemulsification is a thermodynamically favoured process that occurs spontaneously with no/or little energy input.
No homogenizers, no sonicators, no pump or sheers!
MIMICS NATURAL ABSORPTION
O2W improves poor bioavailability by mimicking the naturally occurring mixed micellar transport system of the human body and promoting lymphatic transport.
WHY IS THIS IMPORTANT?
Increased potency This can improve the overall performance of O2W and lead to the higher potency of end-products.
Unlike nanoemulsions, microemulsions are inherently thermodynamically stable.
Upon dilution, O2W forms a microemulsion, in which the oil droplets are fully covered and protected by the hydrophilic interface of the micelles.
The interface is engineered in a way that minimizes the interfacial tension between oil and water and therefore, enhances the stability of the micellar system.
WHY IS THIS IMPORTANT?
No external energy is required The inherent thermodynamic stability means no external source of energy is required to produce or maintain the system.
The hydrophobic interface will protect the active ingredient from degradation in the digestive system and prevents chemical interaction between the active ingredient and the inner layer of packaging.
This means no loss of the active ingredient over time and an increased shelf-life.
A unique characteristic of O2W is that it’s a water-free concentrate system, which is fully dilutable in any volume of water.
WHY IS THIS IMPORTANT?
Increased convenience and shelf-life Water-free systems are more advantageous for producing smaller size dosage forms, smaller packages and smaller storage areas.
They also reduce the risk of product contamination and increase shelf-life.
ENHANCED PERFORMANCE WITH O2W
O2W accelerates onset of action: As a result of the dual absorption pathways, as seen in our study and backed up by literature, there is a faster onset of action.
PEGs diminish cellular uptake: Overall, glycerol esters of fatty acids-based SEDDSs have a three-fold increased cellular uptake than PEG-based SEDDSs. Uptake pathways like receptor-mediated endocytosis and fusion of lipid carriers with the cellular membrane are diminished when using PEGs. Long-chain PEG-surfactant form an inert hydrophilic corona at SEDDS surface that shielded the cationic surface charge thus restraining cell-SEDDS interactions. Glycerol esters of fatty acids-based SEDDSs displaying short-chain fatty acids on the surface, exhibit not only intensified SEDDS–cell interaction but also enhanced membrane disruption.
PEGs inhibit membrane interaction: The PEG-corona not only shields PEG from interacting with cellular membranes but also endosomal membranes. The PEG-corona dramatically hinders endosomal escape after internalization leading to an extensive drug degradation in lysosomes.
PEGs increase emulsification time: In terms of self-emulsification, glycerol esters of fatty acids-based SEDDSs dispersed more rapidly than PEG-SEDDSs.
Contamination: It is feared that toxic impurities from the industrial process might leave traces in the PEG compounds that would be later absorbed into the skin. . This concern is based on how easily PEGs are absorbed by the derma.
PEGs may be contaminated with measurable amounts of ethylene oxide and 1,4-dioxane. The International Agency for Research on Cancer classifies ethylene oxide as a known human carcinogen and 1,4-dioxane as a possible human carcinogen.
Immunogenicity: PEGs can lead to accelerated blood clearance (ABC) of active ingredients. it is increasingly recognized that that patients who take PEGylated medications or have consumed products containing PEG can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). This can actively promote ABC.
ENHANCED SAFETY VIA O2W
Long-term safety: Long-term toxicity study in rats with β-Carotene revealed no safety concerns. (Please see FAQ)
Potential reduction in metabolites: Increase in liver enzymes is one of the most common adverse events with CBD. Promotion of lymphatic transport can potentially reduce the creation of CBD metabolites (7 COOH-CBD and 7 OH-CBD) through hepatic phase 1 metabolism. In vitro data suggest that 7-COOH-CBD could cause serum ALT elevations, causing liver damage. Unlike first generation delivery systems, O2W allows CBD to enter the lymphatic system potentially limiting production of metabolites and adverse drug interactions.
May limit drug interaction: with antipsychotics, beta blockers and opioids. CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes. This key enzyme group metabolizes most of the drugs we consume, including more than 60 percent of marketed meds.
At sufficient dosages, CBD will temporarily deactivate cytochrome P450 enzymes, thereby altering how we metabolize a wide range of compounds, including tetrahydrocannabinol (THC), which causes the high that cannabis is famous for.
Pollution: The process to create PEGs involves ethylene oxide and 1,4-dioxane; substances that are not only very harmful but also strong pollutants.
Ethylene oxide is a flammable, colorless gas used to make other chemicals in products like detergents, adhesives, plastics, and even antifreeze. However, it has been classified as a hazardous air pollutant and identified as a potential concern across the US by the environmental protection agency (EPA) and the National Air Toxics Assessment (NATA).
Similarly, 1,4-dioxane is a clear, water miscible, flammable liquid typically found in dyes, greases, and antifreeze. As a synthetic industrial chemical, 1,4-dioxane is an emerging groundwater contaminant that is considered to migrate in groundwater quicker than other contaminants. Given its physical and chemical properties, 1,4-dioxane creates many challenges for its characterization and treatment in water filtration systems due to its high mobility and low biodegradability.
Biodegradability: Along with the low biodegradability of 1,4-dioxane, PEG compounds themselves are also considered to have low biodegradability. Multiple studies have published that PEG compounds past a specific molecular weight are resistant to biodegradability. This low biodegradability can allow PEG compounds to end up in rivers, streams and oceans.
LESS ENERGY CONSUMPTION WITH O2W
Many emulsion systems have a complex and energy intensive manufacturing process that relies on heavy machinery to induce high mechanical energy and high shear stress to achieve a kinetically stable system.
In contrast, O2W is a thermodynamically stable system that only requires little energy input through a simple manufacturing process. This low energy process reduces our environmental footprint and produces an eco-friendlier product.