A quiet analytical research laboratory at night, racks of glass vials along a dim bench.

Oxidation and Instability

Many valuable actives lose potency before anyone takes them. Thiols such as NAC and glutathione, polyphenols, carotenoids such as astaxanthin, ubiquinol, vitamin C and methionine-containing peptides all oxidize in contact with oxygen, light, heat and trace metals, and the label claim can drift well before expiry.

How oxidation degrades actives

Thiols oxidize to disulfides, turning reduced glutathione into glutathione disulfide and NAC into its dimer. Conjugated systems in carotenoids and polyphenols react with singlet oxygen and free radicals and fragment or isomerize. Ubiquinol, the reduced form of CoQ10, converts to ubiquinone in air. In peptides, methionine, cysteine, tryptophan and histidine residues are the main oxidation sites, and oxidation can change activity. Light accelerates many of these reactions, and trace iron or copper catalyzes them.

Standard mitigations

Formulators use nitrogen flushing, oxygen scavengers, blister packs and opaque containers, chelators such as EDTA, and co-antioxidants such as tocopherols and ascorbyl palmitate. Salt forms and prodrugs can also help, for example S-acetyl glutathione. Each adds cost or complexity, and none protects the active once the pack is opened or the product enters a liquid or cream. Protection that lives in the packaging also depends on consistent handling through distribution, storage and use by the consumer.

How stability is proven

Shelf-life claims rest on long-term and accelerated stability studies under ICH conditions, such as 25 C at 60% relative humidity and 40 C at 75% relative humidity, plus photostability testing. Assay, degradation products and physical attributes are tracked at set time points. For partners, a documented stability advantage is often the most defensible benefit of encapsulation. Degradant identification matters as much as potency loss, because some oxidation products have their own activity or safety profile.

Key facts

Stability testing of new products uses long-term (25 C/60% RH) and accelerated (40 C/75% RH) conditions (ICH Q1A(R2) 2003)
Photostability testing is a separate requirement for light-sensitive products (ICH Q1B 1996)
Methionine, cysteine, histidine and tryptophan are the residues most susceptible to oxidation in protein pharmaceuticals (Li et al. 1995, Biotechnol Bioeng)
L-ascorbic acid is unstable in aqueous formulations and requires low pH to penetrate and remain active (Pinnell et al. 2001, Dermatol Surg)

How our delivery technology applies

Encapsulation moves antioxidant protection from the package into the particle. The active sits in an inner core with limited oxygen diffusion, surrounded by layers that can carry co-antioxidants, chelators or UV-absorbing components. Protection therefore continues after the container is opened and inside aqueous formulas. We quantify it as assay retention and degradant formation under ICH conditions against an unencapsulated control.

Request an ICH stability comparison for your active.