DELIVERY SYSTEMS 63


Overcoming the challenges of ascorbic and azelaic acid


Lisa Lien, Wendy Chen - Corum ABSTRACT


In our previous studies published in the March 2026 issue of Personal Care Magazine,1


we


demonstrated how the next-generation dual- active co-drug molecule, NeoC101™ (INCI: Diascorbyl Azelate), acts as a potent biochemical shield against oxy-ageing. We explored its remarkable ability to support


mitochondrial function by promoting the SOD2 antioxidant defence system and upregulating the cytoprotective HMOX1 gene, thereby neutralizing reactive oxygen species (ROS) and slowing down premature skin ageing. However, for cosmetic formulators globally, a fundamental question remains: How does this specific molecule overcome the long-standing physicochemical limitations of ascorbic acid and azelaic acid to deliver high biological efficacy without the irritation typically associated with high-concentration acid formulations? With the conclusion of our latest in vivo


confocal Raman spectroscopy clinical trials and in vitro 3D epidermal models, this follow- up study decodes the underlying delivery science of diascorbyl azelate. We present exclusive data validating its patented targeted mechanism, demonstrating that the molecule itself is biologically active while also establishing an epidermal reservoir that delivers active metabolites, ascorbic acid and azelaic acid, deep into the dermal-epidermal junction (DEJ) up to 120 µm.


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The formulation bottleneck: the paradox of solubility and penetration Ascorbic acid and azelaic acid are two of the most well-documented dermatological ingredients. Yet, they represent two extremes of formulation nightmares. Traditional native ascorbic acid is highly unstable and extremely hydrophilic (Log P ≈ -2.0), meaning it is effectively repelled by the lipid-rich stratum corneum barrier. Conversely, while lipophilic vitamin C


derivatives (Log P > 5) improve stability, they possess an excessively high affinity for lipids, often becoming trapped within the stratum corneum’s lipid matrix and failing to diffuse into the deeper viable epidermis. Meanwhile, azelaic acid suffers from notoriously poor aqueous solubility, leading to crystallization, limited bioavailability, and significant stinging and burning sensations upon application. To bypass these hurdles, the industry has


traditionally relied on ‘stacking’, the physical combination of high concentrations of active ingredients to offset degradation and limited penetration. However, this brute-force approach frequently results in formulation instability, heavy sensory profiles, and disruption of the skin barrier.


The structural advantage: the amphiphilic molecule Addressing these limitations requires a paradigm


This article presents a next-generation co-drug molecule, NeoC101™ (INCI: Diascorbyl Azelate), developed to overcome the key limitations of ascorbic acid and azelaic acid, including instability, poor penetration, and irritation. By integrating two ascorbic acid units with one azelaic acid core, this amphiphilic structure enables efficient transport across both lipid and aqueous skin environments. Its patented co-drug technology mechanism allows the intact molecule to penetrate the skin barrier and form a controlled epidermal reservoir. Positioned near the 500 Dalton threshold, it functions with a built-in ‘diffusion brake’, ensuring sustained retention and gradual in situ release of active components, rather than rapid transdermal loss. This delivery behaviour is validated through in vitro 3D epidermal models and in vivo confocal Raman spectroscopy, demonstrating controlled accumulation within the skin and targeted delivery to the dermal–epidermal junction (DEJ) at approximately 120 µm depth over 24 hours. At this biologically relevant site, diascorbyl azelate releases ascorbic acid and azelaic acid in a synchronized manner. Clinically, this targeted and sustained delivery translates into enhanced collagen support, strong antioxidant activity, improved brightening, microbiome modulation, and anti-inflammatory effects. Overall, diascorbyl azelate represents a shift from high-dose formulation strategies toward precise molecular engineering for improved efficacy, tolerability, and formulation flexibility


shift in molecular design. Synthesized via enzymatic green chemistry, diascorbyl azelate (MW = 504.4 g/ mol) utilizes an innovative Co-drug mechanism. Its precise architecture features an azelaic acid core esterified with two ascorbic acid molecules at its ends. This structural modification yields several unparalleled physicochemical advantages:


Amphiphilicity (Log P = -0.14) Unlike hydrophilic or highly lipophilic derivatives, diascorbyl azelate possesses a critical partition coefficient of -0.14. This specific polarity profile allows it to efficiently partition into the skin’s lipid bilayers due to its C9 azelaic hydrophobic core,


July 2026 PERSONAL CARE MAGAZINE


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