64 DELIVERY SYSTEMS
while simultaneously maintaining the ability to transit into the deeper, aqueous viable epidermis.
The co-drug technology shielding By esterifying the azelaic acid, the molecule successfully masks the irritating carboxyl groups (-COOH), while keeping the critical 2,3-enediol and gamma-lactone active sites of ascorbic acid completely intact and shielded from oxidation. The preservation of intact ascorbic acid is
particularly critical, as skin cells primarily uptake the active L-ascorbic acid via specific sodium- dependent vitamin C transporters (SVCTs). It quietly penetrates the skin barrier without triggering an inflammatory response, ensuring the payload is perfectly recognized and utilized by the cells upon release.
Molar efficiency (1+2 > 3) Diascorbyl azelate is designed to undergo in situ cleavage within the skin, where a single molecule releases one azelaic acid and two ascorbic acid molecules. This amplified molar yield enables potent biological activity at significantly lower use levels compared to traditional high-concentration formulations.
The 500 Dalton ‘diffusion brake’ & reservoir formation In dermatological science, the traditional ‘500 Dalton rule’ dictates that molecules larger than this threshold struggle to permeate the skin barrier. With a molecular weight of precisely 504.4 g/mol, diascorbyl azelate sits just at this critical boundary. However, instead of hindering absorption, this
specific size acts as a strategic “diffusion brake.” It allows the amphiphilic molecule to successfully enter the stratum corneum but naturally slows its downward transit. This intentionally creates a stable active
Stratum
Corneum Layer
(0-20µm) Viable
Epidermis Layer
(20-80µm)
DEJ Region (80-120µm)
Dermis (120-3000µm) 0h Stratum
Corneum Layer
(0-20µm) Viable
Epidermis Layer
(20-80µm)
DEJ Region (80-120µm)
Dermis (120-3000µm) 8h 10h 12h 24h 2h 4h 6h EPiTRI penetration (Cumulative amount)
800 700 600 500 400 300 200 100 0
0 1 2 3 4 5 6 7 2.5-fold
2% NeoC101 ■ 5% NeoC101 ■ 10% NeoC101 ■
515.7
199.3 21.4 8 9 10 11 12 13 14 15 16 17 18
EPiTRI penetration (% of applied dose) Time (h)
20 15 12.0 10 5 2.7 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time (h) Figure 1: In vitro skin penetration profile of diascrobyl azelate in EpiTRI human skin model
reservoir within the upper layers, providing the exact optimal window of time required for the skin’s endogenous enzymes to initiate the in situ cleavage. Without this built-in molecular brake, the active would either flush through the skin too rapidly or fail to convert efficiently.
Breaking the penetration myth: the reservoir effect (EpiTRI® 3D model) When evaluating active delivery, higher rapid penetration percentages are often mistakenly equated with better efficacy. True sustained-release skincare, however, relies on building a cutaneous ‘reservoir.’ To evaluate this, an in vitro permeation
study using the OECD TG 439-validated EpiTRI reconstructed human epidermis model was conducted (Figure 1). Formulated in an anhydrous propylene
glycol system, diascorbyl azelate demonstrated a remarkable controlled delivery profile over 24 hours. The control molecule, caffeine, exhibited a rapid burst release, with 85% penetrating into the receptor fluid within the first eight hours, reaching 98% at 24 hours. In stark contrast, diascorbyl azelate exhibited 0% penetration into the receptor fluid during the first eight hours across all three tested concentrations (2%, 5%, 10%). At 24 hours, the 2% diascorbyl azelate dose
showed a mere 2.7% total penetration into the receptor fluid. This indicates that the remaining 98.3% of the active payload was flawlessly retained within the stratum corneum and viable epidermis, actively forming a bio-reservoir for continuous sustained release without simply ‘flushing’ through the skin tissue. Furthermore, the study proved that diascorbyl
Figure 2: Spatiotemporal distribution and skin layer penetration of diascrobyl azelate and its released actives
PERSONAL CARE MAGAZINE July 2026
azelate completely breaks the saturation ceiling of traditional acid formulations. When the concentration was increased to 10%, the 24- hour absolute cumulative delivery surged to an
www.personalcaremagazine.com 14 15 16 17 18 19 20 21 22 23 24 9.1 19 20 21 22 23 24 9.3-fold
Percentage of applied dose (%)
Cumulative amount (µg/cm2
)
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