INFORM March 2025

SURFACTANT APPLICATIONS

inform March 2025, Vol. 36 (3) • 15

Almost all previous formulations were only partially dilu table, forming microemulsions when the water content is high. What is unique about Nouraei’s approach is the complete range of dilutability that is possible. When the SMEDDS preconcen trate is mixed with water, it first turns into reverse micelles and then flips into a bi-continuous system. Finally, at high water con tent, it forms direct micelles. All these phase transitions happen without crossing any phase separation boundaries. This full dilutability is essential, Nouraei said, because when you take a capsule, you do not know how much water is in your stomach and intestine. Nouraei also stressed that this flexibility allows for the design and development of multiple dosage forms. FORMULATION CHALLENGES However, formulating such a successful fully dilutable SMEDDS turned out to be quite a challenging and resource-intensive procedure that involved constructing numerous ternary phase diagrams and testing hundreds (or even thousands) of possi ble formulations to map the dilution profile of each candidate formulation. To accelerate the process, Nouraei turned to the HLD-NAC model: the hydrophilic-lipophilic-difference (HLD) and net-average-curvature (NAC) framework. HLD is a set of equations correlating the hydrophobicity of the oil and the surfactants in the SMEDDS, the salinity of the aqueous solution they are to be dropped into, and the tem perature. NAC then interprets the HLD value as the normalized net curvature of the surfactant-oil-water interface. HLD-NAC can thus be used to determine and predict the required type and characteristics of oils and surfactants to use and the mini

mum amount of surfactant required in a SMEDDS to produce a single-phase microemulsion when it is diluted with water. The model also predicts many other outputs such as drop size, type of microemulsion, viscosity, and surface tension. And when there is a problem, like phase separation due to drug-formula tion interactions, the model can tell you what the problem is and how to tweak the components of your SMEDDS to achieve a smooth dilution path with no phase separation. “We used ibuprofen—a non-steroid anti-inflammatory drug—as a model insoluble compound and noticed that since ibuprofen is a polar oil it plays somewhat of a surfactant role itself. The model guided us to use a super-hydrophilic linker in the SMEDDS to restore the full dilutability of the system,” Nouraei said. The results of an animal study showed a significant increase in the absorption and bioavailability of SMEDDS formulated ibuprofen compared to regular tablets. A NEW APPLICATION Since receiving his doctorate, Nouraei became the Founder, Chief Scientific Officer, and Chairman of the Board at Micellae Delivery Systems, where he used the same approach to discover a delivery system for cannabinoids (https://micellae.com). There is no dearth of companies selling upscale canna bis products to upscale millennials promising to deliver just the right amount of mellow buzz with CBD laced seltzers, teas, juices, and gummies. But behind all of that flashy marketing, some pretty hardcore science is required to figure out how to get lipophilic cannabinoids to dissolve in those yuzu and wild berry tonics.