FORMULATING 93
Advanced strategies for retinol stabilization
Nadine Schuelke, Claudia Doberenz, Kathrin Ludwig – Medskin Solutions Dr. Suwelack AG ABSTRACT
Contemporary cosmetic formulation is increasingly shaped by a fundamental paradox: the growing demand for evidence-based actives must be reconciled with their limited stability in conventional aqueous delivery systems. Ingredients such as L-ascorbic acid (vitamin C), retinoids, and peptides are well documented for their biological relevance, yet their integration into creams and serums remains technically challenging due to high water activity, oxidative stress, and thermal sensitivity. Historically, the stabilization of such
labile actives has relied on complex chemical encapsulation strategies or robust preservative systems designed to control microbial growth and limit degradation in water-rich formulations. While effective to a degree, these approaches often restrict the achievable concentration of the active ingredient, increase formulation complexity, or introduce auxiliary substances that complicate formulation design and brand positioning. As a result, formulators are increasingly
confronted with the question of how to preserve both potency and performance without compromising formulation robustness.
Retinol as a model compound for formulation instability All-trans-retinol (C20
H30
mediated oxidation, and thermal degradation. In aqueous liquid systems, the presence
of dissolved oxygen combined with water mobility accelerates degradation pathways, frequently leading to substantial losses in active concentration. Under non-protective conditions, potency reductions exceeding 50% within a short timeframe have been reported, underscoring the limitations of conventional liquid formulations for retinoid delivery. These stability constraints not only affect shelf
life, but also directly impact biological efficacy, as degraded retinol derivatives exhibit reduced or inconsistent activity. Consequently, alternative formulation strategies that decouple active stability from aqueous environments have gained increasing attention within the cosmetic and dermatological industries.
Lyophilization - the technology of freeze-drying Lyophilization is a sophisticated dehydration process that removes solvents, typically water, via sublimation rather than evaporation, thereby preserving the physicochemical integrity of heat- sensitive biological structures and being able to stabilize a formulation in a solid 3d form.1,2,3
O) represents a particularly
illustrative example of this challenge. Its conjugated polyene structure makes the molecule highly susceptible to photoisomerization, radical-
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Thermodynamics and the triple point The scientific basis of freeze-drying is defined by the phase diagram of water, which maps the states of matter - solid, liquid, vapour - as
The cosmetic and dermatological industries are increasingly challenged by the consumer demand for evidence-based actives that are inherently unstable in conventional aqueous formulations, where high water activity, oxidative degradation, and complex stabilization strategies often limit achievable efficacy. All-trans-retinol, while clinically recognized as a gold standard in skin ageing research, exemplifies this challenge due to its pronounced susceptibility to oxidative and thermal degradation in liquid systems. This article examines the use of lyophilization (freeze-drying) as a formulation strategy to enhance the stability of labile actives. The thermodynamic principles governing the freeze-drying cycle are outlined, with a focus on process engineering and ingredient-specific stabilization mechanisms. Particular attention is given to the role of cryoprotectants such as mannitol in preserving structural integrity and preventing matrix collapse. In addition, data from a 12-week clinical investigation of lyophilized retinol beads (‘Retin+’) are presented, demonstrating statistically significant improvements in skin texture, firmness, and radiance
a function of temperature and pressure.4 In
terrestrial ambient conditions, adding heat to ice causes it to melt into liquid water. However, lyophilization exploits a specific thermodynamic coordinate known as the triple point. The triple point of water occurs at exactly 0.01°C (273.16 K) and a partial vapour pressure of 6.11 mbar approximately 4.58 mmHg or 0.00603 atm). At this precise juncture, all three phases, i.e. ice, liquid, and water vapour, coexist in dynamic equilibrium.
The fundamental rule of lyophilization is that
the process must occur below this triple point. If the vapour pressure in the drying chamber is maintained below 6.11 mbar, ice cannot melt into liquid water upon heating; instead, it undergoes sublimation, transitioning directly from the solid phase to the gaseous phase.5 This bypass of the liquid phase is critical for
cosmetic actives. Liquid water acts as a solvent and a plasticizer; its presence allows for the
March 2026 PERSONAL CARE MAGAZINE
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