In this Lab Note, I’ll take you on the journey behind Azelaic Advanced—how it went from an idea to a breakthrough in skincare. We’ll dive into the science, the challenges we faced, and the many experiments that led us to a stable, clear solution. While I can’t reveal every step of the solubilization process, I’ll share as much as possible to explain how we achieved what many considered impossible.
The Spark of an Idea
The idea to solubilize azelaic acid (AZ) sparked about five years ago. Published research unanimously mentions that AZ crystals are notoriously stubborn—they just don’t dissolve easily. To penetrate the skin effectively, AZ needs to dissolve fully, but conventional products typically use high concentrations (10–20%) just to get less than 5% to absorb into the skin.
The undissolved crystals? They’re stuck in their solid form, unable to do anything meaningful. The bigger the crystals, the worse the bioavailability, meaning much of the active ingredient goes to waste.
We saw this as an opportunity. Alyssa and I spent nearly a year poring over studies on drug delivery, solubility, and azelaic acid, creating a list of potential solutions. Little did we know, we were setting ourselves up for years of trial, error, and breakthroughs.
Trial and Error: Delivery Methods
First up: Encapsulation. Liposomes, transferosomes, and the endless "-somes" seemed promising. But, they all hit the same wall—AZ’s solubility. Without dissolving AZ first, they all led to crystals within the structures.
Next, we tried cyclodextrins, cup-like molecules designed to house active ingredients. Sounds perfect, right? Not so fast. AZ still needed to be solubilized before it could work with cyclodextrins. So, we shifted gears to focus solely on solubility.
Cracking the Solubility Code
Research showed that AZ could dissolve under very specific conditions—10% in propylene glycol, 20% in polysorbates, or 30–40% in Ethoxydiglycol (ED) and surfactants. But there was a catch. Using these in high concentrations were too irritating for skin. The best solvent, Cocamidopropyl Dimethylamine, could dissolve 40% AZ but wasn’t safe for leave-on products.
We considered making a cleanser, but that felt unoriginal. We wanted innovation—a way to dissolve 10% AZ for a leave-on treatment.
The Breakthrough: A Chance Discovery
After two years of dead ends, we decided to take a break from solubility and focus on complementary ingredients for redness, pigmentation, and breakouts. While experimenting with a completely unrelated formula, I noticed something peculiar.
One of the beakers contained a clear liquid where an opaque one was expected. The texture was like stiff slime, but when dropped in water, it separated into a thin, oily layer at the bottom. I thought I’d made a mistake. But after repeating the experiment, the phenomenon persisted.
Was I hallucinating?
Alyssa and I couldn’t explain it, but we wondered: could this work with AZ? Alyssa tested the process on azelaic acid, but every attempt produced white crystals—until one day, she showed me a vial of clear, yellow liquid. It was a moment of pure joy. But the next day, the solution crystallised again.
Despite the setback, that glimpse of possibility kept us going. Alyssa refined the process over a gruelling month and cracked it. We achieved a stable, clear solution with 50% dissolved azelaic acid. No PEGs, no glycols, no surfactants—just AZ and our secret Magic Pixie Dust. Hence why we cheekily named this slime AZ-PixieTM
From Solubilization to Serum
Now came the next hurdle: integrating AZ-Pixie into a water-based serum. Adding it to oil, water or glycol caused immediate recrystallization. We needed a clear solution to visually showcase our solubility breakthrough. Adding AZ-Pixie to an opaque cream would obscure the results and make it harder for people to believe in the innovation.
We explored two advanced techniques:
Nanoemulsions: These emulsions create ultra-small droplets (100–500 nanometers), giving them a translucent appearance. However, they require specialized equipment and limit batch sizes—a major drawback for scaling production.
Microemulsions: With even smaller droplet sizes (10–100 nanometers), microemulsions are fully transparent. The downside? They require high concentrations of specialized emulsifiers and produce a thin, watery texture.
We tested dozens of microemulsion emulsifiers, but none worked—until we noticed a similarity between their structures and Potassium Azeloyl Diglycinate, an azelaic acid derivative. Ironically, this derivative became the key to stabilizing AZ-Pixie. By combining it with Azelamide MEA, we created a stable microemulsion.
Fine-Tuning
While performing stability tests we realised that although it is stable at room temperature, the formula crystallised when refrigerated—a major problem in chilly Canada. After reading about microemulsion co-emulsifiers, we decided to test some. Countless trials later, Ethoxydiglycol (ED) emerged as the only possible solution. We didn’t really want to use ED but it is the only ingredient that can maintain the microemulsion and not have a horrible sticky texture. We decided to substitute some of the ED with Pentylene Glycol, Butylene Glycol, and Methylpropanediol, reducing stickiness while maintaining stability.
After countless iterations, we had a clear, stable serum. The final step was to incorporate Alyssa’s carefully chosen ingredients for redness, breakouts, and pigmentation—but those deserve their own Lab Note.
Wrapping Up
Creating Azelaic Advanced was a journey of curiosity, persistence, and creativity. From tackling solubility challenges to pioneering a stable, clear formulation, this product is a testament to the power of science and teamwork.
We’ve packed so much into this Lab Note already, but stay tuned for the next one, where we’ll delve into the remarkable ingredients that complement azelaic acid’s effects.
Until next time, stay curious and keep challenging the impossible.
By: Webster Magcalas