INFORM March 2025

14 • inform March 2025, Vol. 36 (3)

Improving the

Lipophilic compounds have poor solubility in aqueous environments, including our bodies. This is a problem since many small-molecule drug therapies are lipophilic compounds. There is thus a need for new lipid-based drug delivery systems (LBDDS) to enhance the bioavailability of these com pounds. But the choice of biocompatible ingredients for formulating such LBDDS is limited and for mulating them has proven challenging. solubility of lipophilic compounds Diana Gitig

Traditionally, polyethylene glycols (PEG) have been used to aid in lipophilic drug delivery because of their favorable solvent properties. However, PEG are made from petroleum. Beyond not being environ mentally friendly, they have other associated safety concerns. In some cases, the body recognizes them as foreign material and initiates pro duction of anti-PEG antibodies, triggering the release of proinflam matory cytokines, and leading to accelerated blood clearance of the very active ingredients they are supposed to be delivering. They can inadvertently deliver toxic impurities left over from industrial process ing, like the carcinogen ethylene oxide. And there have been reports of PEG inducing hypersensitivity and anaphylaxis. Finding a replace ment composed of biocompatible compounds is thus of paramount importance. To that end, Mehdi Nouraei worked on self-microemulsifying drug delivery systems, or SMEDDS, when he was a doctoral student in Edgar Acosta’s lab at the University of Toronto in Ontario, Canada. SMEDDS are combinations of linkers, surfactants, and oils that sponta neously form microemulsions, with droplet sizes ranging from 10-100 nm, when they contact an aqueous phase. In contrast to emulsions and nanoemulsions, microemulsions never break. Because they are thermodynamically stable, microemulsions always remain in a single phase. DESIRED DILUTABILITY Acosta is a leading expert in developing delivery systems for lipophilic active ingredients. With over 20 years of experience, his team has created numerous biocompatible lecithin-based formulations that have advanced the field. Nouraei’s research project involved developing a fully dilutable SMEDDS platform which, when diluted, would create single-phase microemulsions and deliver ibuprofen at any water concentration, from zero to nearly 100 percent ( https://doi.org/10.1016/j.ijpharm.2021.121237).

• Many important drug therapies have limited use due to their low aqueous solubility. • Lipid-based drug delivery systems have been used effectively to enhance the solubility and increase the bioavailability of hydrophobic active pharmaceutical ingredients. • For food-grade applications, the polyethylene glycols that are popular encapsulation materials will need to be replaced. • One research group used their HLD-NAC model expertise to create a delivery system that exists as a single-phase liquid upon dilution with water and tested it in a variety of applications from drug therapies to food products.